All Publications

@article{renekoopman2009,

title = {Aging, Exercise, and Muscle Protein Metabolism},

author = {René Koopman and René Koopman and Luc J. C. Loon and Luc J. C. Loon},

doi = {10.1152/japplphysiol.91551.2008},

year  = {2009},

date = {2009-06-01},

journal = {Journal of Applied Physiology},

volume = {106},

number = {6},

pages = {2040–2048},

abstract = {Aging is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk of developing chronic metabolic disease. The age-re...},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19321567,

title = {Long-Term Leucine Supplementation Does Not Increase Muscle Mass or Strength in Healthy Elderly Men},

author = {Suzanne Verhoeven and Kristof Vanschoonbeek and Lex B Verdijk and René Koopman and Will K W H Wodzig and Paul Dendale and Luc J C Loon},

doi = {10.3945/ajcn.2008.26668},

issn = {1938-3207},

year  = {2009},

date = {2009-05-01},

journal = {The American journal of clinical nutrition},

volume = {89},

number = {5},

pages = {1468–1475},

abstract = {BACKGROUND: It has been reported that the blunted muscle protein synthetic response to food intake in the elderly can be normalized by increasing the leucine content of a meal.nnOBJECTIVE: The objective was to assess the effect of 3 mo of leucine supplementation on muscle mass and strength in healthy elderly men.nnDESIGN: Thirty healthy elderly men with a mean (+/-SEM) age of 71 +/- 4 y and body mass index (BMI; in kg/m(2)) of 26.1 +/- 0.5 were randomly assigned to either a placebo-supplemented (n = 15) or leucine-supplemented (n = 15) group. Leucine or placebo (2.5 g) was administered with each main meal during a 3-mo intervention period. Whole-body insulin sensitivity, muscle strength (one-repetition maximum), muscle mass (measured by computed tomography and dual-energy X-ray absorptiometry), myosin heavy chain isoform distribution, and plasma amino acid and lipid profiles were assessed before, during, and/or after the intervention period.nnRESULTS: No changes in skeletal muscle mass or strength were observed over time in either the leucine- or placebo-supplemented group. No improvements in indexes of whole-body insulin sensitivity (oral glucose insulin sensitivity index and the homeostasis model assessment of insulin resistance), blood glycated hemoglobin content, or the plasma lipid profile were observed.nnCONCLUSION: Long-term leucine supplementation (7.5 g/d) does not augment skeletal muscle mass or strength and does not improve glycemic control or the blood lipid profile in healthy elderly men. This trial was registered at clinicaltrials.gov as NCT00807508.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19321592,

title = {Poly (ADP-ribose) Polymerase-1-Inhibiting Flavonoids Attenuate Cytokine Release in Blood from Male Patients with Chronic Obstructive Pulmonary Disease or Type 2 Diabetes},

author = {Antje R Weseler and Liesbeth Geraets and Harald J J Moonen and Ralph J F Manders and Luc J C Loon and Herman-Jan Pennings and Emiel F M Wouters and Aalt Bast and Geja J Hageman},

doi = {10.3945/jn.108.102756},

issn = {1541-6100},

year  = {2009},

date = {2009-05-01},

journal = {The Journal of nutrition},

volume = {139},

number = {5},

pages = {952–957},

abstract = {Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P ¡ 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P ¡ or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lexb.verdijk2009,

title = {Protein Supplementation before and after Exercise Does Not Further Augment Skeletal Muscle Hypertrophy after Resistance Training in Elderly Men},

author = {Lex B. Verdijk and Lex B. Verdijk and Richard A. M. Jonkers and Richard A. M. Jonkers and Benjamin G. Gleeson and Benjamin G. Gleeson and Milou Beelen and Milou Beelen and Kenneth Meijer and Kenneth Meijer and Hans Savelberg and Hans H. C. M. Savelberg and Will K. W. H. Wodzig and Will K. W. H. Wodzig and Paul Dendale and Paul Dendale and Paul Dendale and Luc J. C. Loon and Luc J. C. Loon},

doi = {10.3945/ajcn.2008.26626},

year  = {2009},

date = {2009-02-01},

journal = {The American Journal of Clinical Nutrition},

volume = {89},

number = {2},

pages = {608–616},

abstract = {BACKGROUND: Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly. OBJECTIVE: The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. DESIGN: Healthy elderly men (n = 26) aged 72 ± 2 y were randomly assigned to a progressive, 12-wk resistance-type exercise training program with (protein group) or without (placebo group) protein provided before and immediately after each exercise session (3 sessions/wk, 20 g protein/session). One-repetition maximum (1RM) tests were performed regularly to ensure a progressive workload during the intervention. Muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), limb (computed tomography), and muscle fiber (biopsy) level. RESULTS: The 1RM strength increased [almost equal to]25-35% in both groups (P $<$ 0.001). Dual-energy X-ray absorptiometry and computed tomography scans showed similar increases in leg muscle mass (6 ± 1% in both groups; P $<$ 0.001) and in the quadriceps (9 ± 1% in both groups), from 75.9 ± 3.7 and 73.8 ± 3.2 to 82.4 ± 3.9 and 80.0 ± 3.0 cm$^2$ in the placebo and protein groups, respectively (P $<$ 0.001). Muscle fiber hypertrophy was greater in type II (placebo: 28 ± 6%; protein: 29 ± 4%) than in type I (placebo: 5 ± 4%; protein: 13 ± 6%) fibers, but the difference between groups was not significant. CONCLUSION: Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. This trial was registered at clinicaltrials.gov as NCT00744094.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19448045,

title = {Slowly Digestible Carbohydrate Sources Can Be Used to Attenuate the Postprandial Glycemic Response to the Ingestion of Diabetes-Specific Enteral Formulas},

author = {K Vanschoonbeek and M Lansink and K M J Laere and J M G Senden and L B Verdijk and L J C Loon},

doi = {10.1177/0145721709335466},

issn = {0145-7217},

year  = {2009},

date = {2009-01-01},

journal = {The Diabetes educator},

volume = {35},

number = {4},

pages = {631–640},

abstract = {PURPOSE: The purpose of this study is to compare the glycemic and insulinemic responses following the ingestion of recently developed diabetes-specific enteral formulas versus a standard and a high-fat formula.nnMETHODS: Fifteen type 2 diabetes patients were selected to participate in a randomized, double-blind, crossover study. Two enteral formulas (47 energy percent [En%] carbohydrate, 34En% fat, and 4 g fiber/200 mL) were defined with either isomaltulose (formula 1) or sucromalt (formula 2) as the main carbohydrate source. For comparison, an isoenergetic diabetes-specific, high-fat (33En% carbohydrate, 50En% fat, 2.9 g fiber/200 mL) and a standard formula (55En% carbohydrate, 30En% fat, 2.8 g fiber/200 mL) were tested.nnRESULTS: Ingestion of formulas 1 and 2 and the high-fat formula resulted in an attenuated blood glucose response when compared with the standard formula (P ¡ .05). In accordance, peak plasma glucose concentrations were significantly lower when compared with the standard formula (189 +/- 3.6 mg/dL [10.5 +/- 0.2 mmol/L], 196.2 +/- 3.6 mg/dL [10.9 +/- 0.2 mmol/L], 187.2 +/- 3.6 mg/dL [10.4 +/- 0.2 mmol/L], and 237.6 +/- 3.6 mg/dL [13.2 +/- 0.2 mmol/L], respectively). Plasma insulin responses were lower after consumption of the newly developed and high-fat formulas. Ingestion of the high-fat formula resulted in a greater postprandial triglyceride response (P ¡ .05).nnCONCLUSIONS: Diabetes-specific enteral formulas rich in slowly digestible carbohydrate sources can be equally effective in attenuating the postprandial blood glucose response as low-carbohydrate, high-fat enteral formulas without elevating the plasma triglyceride response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{jaspers2009,

title = {Protein Hydrolysate Co-Ingestion Does Not Modulate 24 h Glycemic Control in Long-Standing Type 2 Diabetes Patients},

author = {Richard T. Jaspers and Ralph Manders and Ralph J. F. Manders and Stephan Praet and Stephan F. E. Praet and Max Vikström and M H Vikström and Wim H. M. Saris and W. H. M. Saris and Wim H. M. Saris and W. H. M. Saris and W. H. M. Saris and Luc J. C. Loon and Luc J. C. Loon and L. J. C. Loon},

doi = {10.1038/sj.ejcn.1602891},

year  = {2009},

date = {2009-01-01},

journal = {European Journal of Clinical Nutrition},

volume = {63},

number = {1},

pages = {121–126},

abstract = {Protein hydrolysate co-ingestion does not modulate 24h glycemic control in long-standing type 2 diabetes patients},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{lexb.verdijk2009a,

title = {Skeletal Muscle Hypertrophy Following Resistance Training Is Accompanied by a Fiber Type–Specific Increase in Satellite Cell Content in Elderly Men},

author = {Lex B. Verdijk and Benjamin G. Gleeson and Richard A. M. Jonkers and Kenneth Meijer and Hans Savelberg and Paul Dendale and Luc J. C. Loon},

doi = {10.1093/gerona/gln050},

year  = {2009},

date = {2009-01-01},

journal = {Journals of Gerontology Series A-biological Sciences and Medical Sciences},

volume = {64},

number = {3},

pages = {332–339},

abstract = {We determined muscle fiber type–specific hypertrophy and changes in satellite cell (SC) content following a 12-week resistance training program in 13 healthy, elderly men (72 ± 2 years). Leg strength and body composition (dual-energy X-ray absorptiometry and computed tomography) were assessed, and muscle biopsy samples were collected. Leg strength increased 25%–30% after training (p $<$ .001). Leg lean mass and quadriceps cross-sectional area increased 6%–9% (p $<$ .001). At baseline, mean fiber area and SC content were smaller in the Type II versus Type I muscle fibers (p $<$ .01). Following training, Type II muscle fiber area increased from 5,438 ± 319 to 6,982 ± 503 μm2 (p $<$ .01). Type II muscle fiber SC content increased from 0.048 ± 0.003 to 0.084 ± 0.008 SCs per fiber (p $<$ .001). No changes were observed in the Type I muscle fibers. In older adults, skeletal muscle tissue is still capable of inducing SC proliferation and differentiation, resulting in Type II muscle fiber hypertrophy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19031334,

title = {One-Repetition Maximum Strength Test Represents a Valid Means to Assess Leg Strength in Vivo in Humans},

author = {Lex B Verdijk and Luc Loon and Kenneth Meijer and Hans H C M Savelberg},

doi = {10.1080/02640410802428089},

issn = {0264-0414},

year  = {2009},

date = {2009-01-01},

journal = {Journal of sports sciences},

volume = {27},

number = {1},

pages = {59–68},

abstract = {Skeletal muscle strength is often determined to evaluate the adaptive response to an exercise intervention programme. Although dynamometry is considered the "gold standard" for the assessment of muscle strength in vivo, one-repetition maximum (1-RM) testing performed on training-specific equipment is more commonly applied. We assessed the validity of specific knee extension 1-RM testing by comparison with dynamometry in a heterogeneous population (n=55). All participants performed 1-RM tests on regular leg extension and leg press machines. Additionally, isometric (at seven different knee angles) and isokinetic (at four different velocities) knee extension peak torques were determined. Pearson's r was calculated for the relationship between 1-RM data and peak torques for the entire population and for subgroups defined by age and gender. One-repetition maximum strength correlated strongly with the dynamometer results. One-repetition maximum leg extension correlated more strongly with peak torques than did 1-RM leg press (0.78¡or=r¡or=0.88 vs. 0.72¡or=r¡or=0.77; P¡0.001). Similar correlations were observed in all subgroups. We conclude that 1-RM testing represents a valid means to assess leg muscle strength in vivo in young and elderly men and women. Considering the importance of training specificity in strength assessment, we argue that 1-RM testing can be applied to assess changes in leg muscle strength following an exercise intervention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19092695,

title = {Resistance Exercise Increases Postprandial Muscle Protein Synthesis in Humans},

author = {Oliver C Witard and Michael Tieland and Milou Beelen and Kevin D Tipton and Luc J C Loon and René Koopman},

doi = {10.1249/MSS.0b013e3181844e79},

issn = {1530-0315},

year  = {2009},

date = {2009-01-01},

journal = {Medicine and science in sports and exercise},

volume = {41},

number = {1},

pages = {144–154},

abstract = {PURPOSE: We examined the impact of an acute bout of resistance-type exercise on mixed muscle protein synthesis in the fed state.nnMETHODS: After a standardized breakfast, 10 untrained males completed a single, unilateral lower-limb resistance-type exercise session. A primed, continuous infusion of l-[ring-C6]phenylalanine was combined with muscle biopsy collection from both the exercised (Ex) and the nonexercised (NEx) leg to assess the impact of local muscle contractions on muscle protein synthesis rates after food intake. Western blotting with phosphospecific and pan antibodies was used to determine the phosphorylation status of AMP-activated kinase (AMPK), 4E-binding protein (4E-BP1), mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase (S6K1).nnRESULTS: Muscle protein synthesis rates were approximately 20% higher in Ex compared with NEx (0.098% +/- 0.005% vs 0.083% +/- 0.002%.h, respectively, P ¡ 0.01). In the fed state, resistance-type exercise did not elevate AMPK phosphorylation. However, the phosphorylation status of 4E-BP1 was approximately 20% lower after cessation of exercise in Ex compared with NEx (P ¡ 0.05). Conversely, 4E-BP1 phosphorylation was significantly higher in Ex compared with NEx after 6 h of recovery (P ¡ 0.05) with no changes in mTOR phosphorylation. S6 phosphorylation was greater in Ex versus NEx after cessation of exercise (P ¡ 0.05), although S6K1 phosphorylation at T was not up-regulated (P ¿ 0.05).nnCONCLUSION: We conclude that resistance-type exercise performed in a fed state further elevates postprandial muscle protein synthesis rates, which is accompanied by an increase in S6 and 4E-BP1 phosphorylation state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{miloubeelen2008,

title = {Coingestion of Carbohydrate and Protein Hydrolysate Stimulates Muscle Protein Synthesis during Exercise in Young Men, with No Further Increase during Subsequent Overnight Recovery},

author = {Milou Beelen and Michael Tieland and Annemie P. Gijsen and Hanne Vandereyt and Arie K. Kies and H. Kuipers and Wim H. M. Saris and René Koopman and Luc J. C. Loon},

doi = {10.3945/jn.108.092924},

year  = {2008},

date = {2008-11-01},

journal = {Journal of Nutrition},

volume = {138},

number = {11},

pages = {2198–2204},

abstract = {We investigated the effect of carbohydrate and protein hydrolysate ingestion on whole-body and muscle protein synthesis during a combined endurance and resistance exercise session and subsequent overnight recovery. Twenty healthy men were studied in the evening after consuming a standardized diet throughout the day. Subjects participated in a 2-h exercise session during which beverages containing both carbohydrate (0.15 g.kg -1 .h -1 ) and a protein hydrolysate (0.15 g.kg -1 .h -1 ) (C+P},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18344386,

title = {Four Weeks' Corticosteroid Inhalation Does Not Augment Maximal Power Output in Endurance Athletes},

author = {H Kuipers and G A C Van't Hullenaar and B M Pluim and S E Overbeek and O De Hon and E J Van Breda and L C Van Loon},

doi = {10.1136/bjsm.2007.042572},

issn = {1473-0480},

year  = {2008},

date = {2008-11-01},

journal = {British journal of sports medicine},

volume = {42},

number = {11},

pages = {868–871},

abstract = {OBJECTIVE: To assess possible ergogenic properties of corticosteroid administration.nnDESIGN: A balanced, double-blind, placebo-controlled design was used.nnPARTICIPANTS: 28 well-trained cyclists and rowers.nnINTERVENTION: 4 weeks' daily inhalation of 800 microg budesonide or placebo.nnMAIN OUTCOME MEASUREMENTS: The subjects performed three incremental cycle ergometer tests until exhaustion, before and after 2 and 4 weeks of placebo or budesonide administration, to measure maximal power output (W(max)). Once a week they filled in a profile of mood state (POMS) questionnaire.nnRESULTS: There was no significant difference in W(max) between the placebo (376 (SD 25) W) and the corticosteroid group (375 (36) W) during the preintervention test, and there were no significant changes in either group after 2 and 4 weeks of intervention. No effect of the intervention on mood state was found.nnCONCLUSION: 4 weeks of corticosteroid or placebo inhalation in healthy, well-trained athletes did not affect maximal power output or mood state. Hence no ergogenic properties of 4 weeks' corticosteroid administration could be demonstrated, which corroborates previous studies of short-term corticosteroid administration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18709353,

title = {Intravenous AICAR Administration Reduces Hepatic Glucose Output and Inhibits Whole Body Lipolysis in Type 2 Diabetic Patients},

author = {H Boon and M Bosselaar and S F E Praet and E E Blaak and W H M Saris and A J M Wagenmakers and S L McGee and C J Tack and P Smits and M Hargreaves and L J C Loon},

doi = {10.1007/s00125-008-1108-7},

issn = {0012-186X},

year  = {2008},

date = {2008-10-01},

journal = {Diabetologia},

volume = {51},

number = {10},

pages = {1893–1900},

abstract = {AIMS/HYPOTHESIS: The 5'-AMP-activated protein kinase (AMPK) pathway is intact in type 2 diabetic patients and is seen as a target for diabetes treatment. In this study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in type 2 diabetic patients.nnMETHODS: Stable isotope methodology and blood and muscle biopsy sampling were applied to assess blood glucose and fatty acid kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1)) and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI 28 +/- 1 kg/m(2)).nnRESULTS: Plasma glucose rate of appearance (R (a)) was reduced following AICAR administration, while plasma glucose rate of disappearance (R (d)) was similar in the AICAR and control test. Consequently, blood glucose disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR infusion (p ¡ 0.001). Accordingly, a greater decline in plasma glucose concentration was observed following AICAR infusion (p ¡ 0.001). Plasma NEFA R (a) and R (d) were both significantly reduced in response to AICAR infusion, and were accompanied by a significant decline in plasma NEFA concentration. Although AMPK phosphorylation in skeletal muscle was not increased, we observed a significant increase in acetyl-CoA carboxylase phosphorylation (p ¡ 0.001).nnCONCLUSIONS/INTERPRETATION: The i.v. administration of AICAR reduces hepatic glucose output, thereby lowering blood glucose concentrations in vivo in type 2 diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18430966,

title = {Protein Coingestion Stimulates Muscle Protein Synthesis during Resistance-Type Exercise},

author = {Milou Beelen and René Koopman and Annemie P Gijsen and Hanne Vandereyt and Arie K Kies and Harm Kuipers and Wim H M Saris and Luc J C Loon},

doi = {10.1152/ajpendo.00774.2007},

issn = {0193-1849},

year  = {2008},

date = {2008-07-01},

journal = {American journal of physiology. Endocrinology and metabolism},

volume = {295},

number = {1},

pages = {E70–E77},

abstract = {In contrast to the effect of nutritional intervention on postexercise muscle protein synthesis, little is known about the potential to modulate protein synthesis during exercise. This study investigates the effect of protein coingestion with carbohydrate on muscle protein synthesis during resistance-type exercise. Ten healthy males were studied in the evening after they consumed a standardized diet throughout the day. Subjects participated in two experiments in which they ingested either carbohydrate or carbohydrate with protein during a 2-h resistance exercise session. Subjects received a bolus of test drink before and every 15 min during exercise, providing 0.15 g x kg(-1) x h(-1) carbohydrate with (CHO + PRO) or without (CHO) 0.15 g x kg(-1) x h(-1) protein hydrolysate. Continuous intravenous infusions with l-[ring-(13)C(6)]phenylalanine and l-[ring-(2)H(2)]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body and muscle protein synthesis rates during exercise. Protein coingestion lowered whole body protein breakdown rates by 8.4 +/- 3.6% (P = 0.066), compared with the ingestion of carbohydrate only, and augmented protein oxidation and synthesis rates by 77 +/- 17 and 33 +/- 3%, respectively (P ¡ 0.01). As a consequence, whole body net protein balance was negative in CHO, whereas a positive net balance was achieved after the CHO + PRO treatment (-4.4 +/- 0.3 vs. 16.3 +/- 0.4 micromol phenylalanine x kg(-1) x h(-1), respectively; P ¡ 0.01). In accordance, mixed muscle protein fractional synthetic rate was 49 +/- 22% higher after protein coingestion (0.088 +/- 0.012 and 0.060 +/- 0.004%/h in CHO + PRO vs. CHO treatment, respectively; P ¡ 0.05). We conclude that, even in a fed state, protein coingestion stimulates whole body and muscle protein synthesis rates during resistance-type exercise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{jaspers2008,

title = {The Muscle Protein Synthetic Response to Carbohydrate and Protein Ingestion Is Not Impaired in Men with Longstanding Type 2 Diabetes},

author = {Richard T. Jaspers and Ralph J. F. Manders and René Koopman and Milou Beelen and Annemie P. Gijsen and Will K. W. H. Wodzig and Wim H. M. Saris and Luc J. C. Loon},

doi = {10.1093/jn/138.6.1079},

year  = {2008},

date = {2008-06-01},

journal = {Journal of Nutrition},

volume = {138},

number = {6},

pages = {1079–1085},

abstract = {Protein ingestion stimulates muscle protein synthesis and improves net muscle protein balance. Insulin resistance has been suggested to result in a reduced muscle protein synthetic response to food intake. As such, we hypothesized that type 2 diabetes patients have a impaired muscle protein synthetic response to food ingestion. To test this hypothesis, 10 male type 2 diabetes patients using their normal oral glucose-lowering medication (68 +/- 2 y) and 10 matched, normoglycemic men (65 +/- 2 y) were randomly assigned to 2 crossover treatments in which whole body and muscle protein synthesis were measured following the consumption of either carbohydrate (CHO) or carbohydrate with a protein hydrolysate (CHO+PRO). Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied and blood and muscle samples were collected to assess whole-body protein balance and mixed muscle protein fractional synthetic rate over a 6-h period. Whole-body phenylalanine and tyrosine flux were higher after the CHO+PRO treatment compared with the CHO treatment in the diabetes and control group (P $<$ 0.01). Protein balance was negative following CHO but positive following CHO+PRO treatment in both groups. Muscle protein synthesis rates were higher in both groups following the CHO+PRO (0.086 +/- 0.014%/h) treatment than in the CHO treatment (0.040 +/- 0.003%/h; P $<$ 0.01) with no difference between the diabetes patients and normoglycemic controls. We conclude that the muscle protein synthetic response to CHO or CHO+PRO ingestion is not substantially impaired in longstanding, type 2 diabetes patients treated with oral blood glucose-lowering medication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18297259,

title = {Brisk Walking Compared with an Individualised Medical Fitness Programme for Patients with Type 2 Diabetes: A Randomised Controlled Trial},

author = {S F E Praet and E S J Rooij and A Wijtvliet and L J M Boonman-de Winter and Th Enneking and H Kuipers and C D A Stehouwer and L J C Loon},

doi = {10.1007/s00125-008-0950-y},

issn = {0012-186X},

year  = {2008},

date = {2008-05-01},

journal = {Diabetologia},

volume = {51},

number = {5},

pages = {736–746},

abstract = {AIMS/HYPOTHESIS: Structured exercise is considered a cornerstone in type 2 diabetes treatment. However, adherence to combined resistance and endurance type exercise or medical fitness intervention programmes is generally poor. Group-based brisk walking may represent an attractive alternative, but its long-term efficacy as compared with an individualised approach such as medical fitness intervention programmes is unknown. We compared the clinical benefits of a 12-month exercise intervention programme consisting of either brisk walking or a medical fitness programme in type 2 diabetes patients.nnMETHODS: We randomised 92 type 2 diabetes patients (60 +/- 9 years old) to either three times a week of 60 min brisk walking (n = 49) or medical fitness programme (n = 43). Primary outcome was the difference in changes in HbA1c values at 12 months. Secondary outcomes were differences in changes in blood pressure, plasma lipid concentrations, insulin sensitivity, body composition, physical fitness, programme adherence rate and health-related quality of life.nnRESULTS: After 12 months, 18 brisk walking and 19 medical fitness participants were still actively participating. In both programmes, 50 and 25% of the dropout was attributed to overuse injuries and lack of motivation, respectively. Intention-to-treat analyses showed no important differences between brisk walking and medical fitness programme in primary or secondary outcome variables.nnCONCLUSIONS/INTERPRETATION: The prescription of group-based brisk walking represents an equally effective intervention to modulate glycaemic control and cardiovascular risk profile in type 2 diabetes patients when compared with more individualised medical fitness programmes. Future exercise intervention programmes should anticipate the high attrition rate due to overuse injuries and motivation problems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18426822,

title = {Early or Advanced Stage Type 2 Diabetes Is Not Accompanied by in Vivo Skeletal Muscle Mitochondrial Dysfunction},

author = {H M De Feyter and N M A Broek and S F E Praet and K Nicolay and L J C Loon and J J Prompers},

doi = {10.1530/EJE-07-0756},

issn = {1479-683X},

year  = {2008},

date = {2008-05-01},

journal = {European journal of endocrinology},

volume = {158},

number = {5},

pages = {643–653},

abstract = {OBJECTIVE: Several lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes.nnMETHODS: Ten long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using (31)P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel (1)H MRS.nnRESULTS: IMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The(31)P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups.nnCONCLUSIONS: The finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17697406,

title = {Co-Ingestion of Leucine with Protein Does Not Further Augment Post-Exercise Muscle Protein Synthesis Rates in Elderly Men},

author = {René Koopman and Lex B Verdijk and Milou Beelen and Marchel Gorselink and Arie Nieuwenhuijzen Kruseman and Anton J M Wagenmakers and Harm Kuipers and Luc J C Loon},

doi = {10.1017/S0007114507812013},

issn = {0007-1145},

year  = {2008},

date = {2008-03-01},

journal = {The British journal of nutrition},

volume = {99},

number = {3},

pages = {571–580},

abstract = {Leucine has been suggested to have the potential to modulate muscle protein metabolism by increasing muscle protein synthesis. The objective of this study was to investigate the surplus value of the co-ingestion of free leucine with protein hydrolysate and carbohydrate following physical activity in elderly men. Eight elderly men (mean age 73 +/- 1 years) were randomly assigned to two cross-over treatments consuming either carbohydrate and protein hydrolysate (CHO+PRO) or carbohydrate, protein hydrolysate with additional leucine (CHO+PRO+leu) after performing 30 min of standardized physical activity. Primed, continuous infusions with L-[ring-(13)C(6)]phenylalanine and L-[ring-(2)H(2)]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover as well as protein fractional synthetic rate in the vastus lateralis muscle over a 6 h period. Whole-body protein breakdown and synthesis rates were not different between treatments. Phenylalanine oxidation rates were significantly lower in the CHO+PRO+leu v. CHO+PRO treatment. As a result, whole-body protein balance was significantly greater in the CHO+PRO+leu compared to the CHO+PRO treatment (23.8 (SEM 0.3) v. 23.2 (SEM 0.3) micromol/kg per h, respectively; P ¡ 0.05). Mixed muscle fractional synthetic rate averaged 0.081 (SEM 0.003) and 0.082 (SEM 0.006) %/h in the CHO+PRO+leu and CHO+PRO treatment, respectively (NS). Co-ingestion of leucine with carbohydrate and protein following physical activity does not further elevate muscle protein fractional synthetic rate in elderly men when ample protein is ingested.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18089694,

title = {Calpain-10 Gene and Protein Expression in Human Skeletal Muscle: Effect of Acute Lipid-Induced Insulin Resistance and Type 2 Diabetes},

author = {L Norton and T Parr and K Chokkalingam and R G Bardsley and H Ye and G I Bell and M M A L Pelsers and L J C Loon and K Tsintzas},

doi = {10.1210/jc.2007-1981},

issn = {0021-972X},

year  = {2008},

date = {2008-03-01},

journal = {The Journal of clinical endocrinology and metabolism},

volume = {93},

number = {3},

pages = {992–998},

abstract = {OBJECTIVE: Our objective was to investigate the effect of lipid-induced insulin resistance and type 2 diabetes on skeletal muscle calpain-10 mRNA and protein levels.nnRESEARCH DESIGN AND METHODS: In the first part of this study, 10 healthy subjects underwent hyperinsulinemic euglycemic (4.5 mmol/liter) clamps for 6 h with iv infusion of either saline or a 20% Intralipid emulsion (Fresenius Kabi AG, Bad Homburg, Germany). Skeletal muscle biopsies were taken before and after 3- and 6-h insulin infusion and analyzed for calpain-10 mRNA and protein expression. In the second part of the study, muscle samples obtained after an overnight fast in 10 long-standing, sedentary type 2 diabetes patients, 10 sedentary, weight-matched, normoglycemic controls, and 10 age-matched, endurance-trained cyclists were analyzed for calpain-10 mRNA and protein content.nnRESULTS: Intralipid infusion in healthy subjects reduced whole body glucose disposal by approximately 50% (P¡0.001). Calpain-10 mRNA (P=0.01) but not protein content was reduced after 6-h insulin infusion in both the saline and Intralipid emulsion trials. Skeletal muscle calpain-10 mRNA and protein content did not differ between the type 2 diabetes patients and normoglycemic controls, but there was a strong trend for total calpain-10 protein to be greater in the endurance-trained athletes (P=0.06).nnCONCLUSIONS: These data indicate that skeletal muscle calpain-10 expression is not modified by insulin resistance per se and suggest that hyperinsulinemia and exercise training may modulate human skeletal muscle calpain-10 expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18183362,

title = {Exercise: The Brittle Cornerstone of Type 2 Diabetes Treatment},

author = {S F E Praet and L J C Loon},

doi = {10.1007/s00125-007-0910-y},

issn = {0012-186X},

year  = {2008},

date = {2008-03-01},

journal = {Diabetologia},

volume = {51},

number = {3},

pages = {398–401},

abstract = {Regular exercise has been recommended for diabetes patients for many years; however, it is not widely used clinically. This may be because of high costs, lack of reimbursement, low compliance and/or absence of proper infrastructure. Alternatively, structured exercise therapy may be underutilised because current guidelines do not include detailed information on the preferred type and intensity of exercise that should be applied to maximise the benefits of exercise for different subgroups of patients with type 2 diabetes. Based on available evidence and our own clinical research experience this article proposes that exercise therapy in type 2 diabetes might be more effective if (1) cardiac rehabilitation programmes served as a model for 'pre-cardiac diabetes rehabilitation'; (2) resistance exercise were prescribed for sarcopenic or severely deconditioned type 2 diabetes patients; and (3) a multidisciplinary approach and continued exercise training under personal supervision became standard therapy. Nevertheless, more clinical research is warranted to establish the efficacy of an approach that takes into account type 2 diabetes subpopulations at different stages of the disease and with different levels of comorbidity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18230822,

title = {Long-Standing, Insulin-Treated Type 2 Diabetes Patients with Complications Respond Well to Short-Term Resistance and Interval Exercise Training},

author = {S F E Praet and R A M Jonkers and G Schep and C D A Stehouwer and H Kuipers and H A Keizer and L J Loon},

doi = {10.1530/EJE-07-0169},

issn = {1479-683X},

year  = {2008},

date = {2008-02-01},

journal = {European journal of endocrinology},

volume = {158},

number = {2},

pages = {163–172},

abstract = {OBJECTIVE: To determine the feasibility and the benefits of combined resistance and interval exercise training on phenotype characteristics and skeletal muscle function in deconditioned, type 2 diabetes (T2D) patients with polyneuropathy.nnDESIGN: Short-term, single-arm intervention trial.nnMETHODS: Eleven male T2D patients (age: 59.1+/-7.5 years; body mass index: 32.2+/-4.0 kg/m2) performed progressive resistance and interval exercise training thrice a week for 10 weeks. Besides primary diabetes outcome measures, muscle strength (MUST), maximal workload capacity (Wmax), whole-body peak oxygen uptake (VO2peak) and muscle oxidative capacity (MUOX), intramyocellular lipid (IMCL) and glycogen (IMCG) storage, and systemic inflammation markers were determined before and after training. Daily exogenous insulin requirements (EIR) and historic individualized EIR were gathered and analysed.nnRESULTS: MUST and Wmax increased with 17% (90% confidence intervals 9-24%) and 14% (6-21) respectively. Furthermore, mean arterial blood pressure declined with 5.5 mmHg (-9.7 to -1.4). EIR dropped with 5.0 IU/d (-11.5 to 1.5) compared with baseline. A decline of respectively -0.7 mmol/l (-2.9 to 1.5) and -147 micromol/l (-296 to 2) in fasting plasma glucose and non-esterified fatty acids concentrations were observed following the intervention, but these were not accompanied by changes in VO2peak, MUOX, IMCL or IMCG, and blood glycolysated haemoglobin, adiponectin, tumor necrosis factor-alpha and/or cholesterol concentrations.nnCONCLUSION: Short-term resistance and interval exercise training is feasible in deconditioned T2D patients with polyneuropathy and accompanied by moderate improvements in muscle function and blood pressure. Such a specific exercise regimen may provide a better framework for future exercise intervention programmes in the treatment of deconditioned T2D patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mauricem.a.l.pelsers2008,

title = {The Role of Membrane Fatty-Acid Transporters in Regulating Skeletal Muscle Substrate Use during Exercise},

author = {Maurice M. A. L. Pelsers and Trent Stellingwerff and Luc J. C. Loon},

doi = {10.2165/00007256-200838050-00003},

year  = {2008},

date = {2008-01-01},

journal = {Sports Medicine},

volume = {38},

number = {5},

pages = {387–399},

abstract = {While endogenous carbohydrates form the main substrate source during high-intensity exercise, long-chain fatty acids (LCFA) represent the main substrate source during more prolonged low- to moderate-intensity exercise. Adipose tissue lipolysis is responsible for the supply of LCFA to the contracting muscle. Once taken up by skeletal muscle tissue, LCFA can either serve as a substrate for oxidative phosphorylation or can be directed towards esterification into triacylglycerol. Myocellular uptake of LCFA comprises a complex and incompletely understood process. Although LCFA can enter the cell via passive diffusion, more recent reports indicate that LCFA uptake is tightly regulated by plasma membrane-located transport proteins (fatty acid translocase [FAT/CD36], plasmalemmal-located fatty acid binding protein [FABPpm] and fatty acid transport protein [FATP]). Depending on cardiac and skeletal muscle energy demands, some of these LCFA transporters can translocate rapidly from intracellular pools to the plasma membrane to allow greater LCFA uptake. This translocation process can be induced by insulin and/or muscle contraction. However, the precise signalling pathways responsible for activating the translocation machinery remain to be elucidated. This article will provide an overview on the effects of diet, acute exercise and exercise training on the expression and/or translocation of the various LCFA transporters in skeletal muscle tissue (FAT/CD36, FABPpm, FATP).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18046185,

title = {A Single Session of Resistance Exercise Induces Oxidative Damage in Untrained Men},

author = {Saskia J Rietjens and Milou Beelen and Rene Koopman and Luc J C VAN Loon and Aalt Bast and Guido R M M Haenen},

doi = {10.1249/mss.0b013e318157936d},

issn = {0195-9131},

year  = {2007},

date = {2007-12-01},

journal = {Medicine and science in sports and exercise},

volume = {39},

number = {12},

pages = {2145–2151},

abstract = {PURPOSE: During exercise, the production of reactive oxygen and nitrogen species significantly increases. The aim of the present study was to investigate the effects of a single session of resistance exercise on antioxidant capacity, oxidative damage, and inflammation.nnMETHODS: Muscle biopsies, urine, and blood samples were collected from seven healthy men before and after a single bout of resistance exercise.nnRESULTS: A single session of resistance exercise was found to induce oxidative damage, as shown by a 40% increase in the concentration of urinary F2alpha-isoprostanes (P ¡ 0.05). Total antioxidant capacity of plasma increased 16% (P ¡ 0.05). This increase seemed to be predominantly attributable to an increase in plasma uric acid concentrations of 53% (P ¡ 0.05). Similar to uric acid, but to a relatively much smaller extent, vitamin C and vitamin E levels in plasma were also elevated (P ¡ 0.05). Moreover, the erythrocyte glutathione (GSH) [corrected] concentration increased 47% during exercise (P ¡ 0.05). Also in skeletal muscle, uric acid levels were found to increase after exercise (P ¡ 0.05). Moreover, 30 min after exercise, skeletal muscle glutathione S-transferase (GST) and glutathione reductase activity increased 28 and 42%, respectively (P ¡ 0.05). Skeletal muscle reduced GSH [corrected] and GSH [corrected] disulphide (GSSG) concentrations were not affected by exercise. The Nuclear Factor kappa B (NF-kappaB) activity in peripheral blood mononuclear cells (PBMC) was not increased by exercise, indicating that a NF-kappaB-mediated inflammatory response does not occur.nnCONCLUSION: We conclude that a single session of resistance exercise induces oxidative damage despite an adaptive increase in antioxidant capacity of blood and skeletal muscle.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18046187,

title = {Substrate Source Use in Older, Trained Males after Decades of Endurance Training},

author = {Hanneke Boon and Richard A M Jonkers and Rene Koopman and Ellen E Blaak and Wim H M Saris and Anton J M Wagenmakers and Luc J C VAN Loon},

doi = {10.1249/mss.0b013e3181572ace},

issn = {0195-9131},

year  = {2007},

date = {2007-12-01},

journal = {Medicine and science in sports and exercise},

volume = {39},

number = {12},

pages = {2160–2170},

abstract = {PURPOSE: The purpose of this study was to compare substrate source use in older, long-term exercising, endurance-trained males with sedentary controls.nnMETHODS: [U-C]palmitate and [6,6-H2]glucose tracers were applied to assess plasma free fatty acid (FFA) and glucose oxidation rates, and to estimate muscle- and/or lipoprotein-derived triacylglycerol (TG) and muscle glycogen use. Subjects were 10 long-term exercising, endurance-trained males and 10 sedentary controls (age 57 +/- 1 and 60 +/- 2 yr, respectively). Muscle biopsy samples were collected before and after exercise to assess muscle fiber type-specific intramyocellular lipid and glycogen content.nnRESULTS: During exercise, plasma palmitate Ra, Rd, and Rox were significantly greater in the trained subjects compared with the controls (Ra: 0.36 +/- 0.02 and 0.25 +/- 0.02; Rd: 0.36 +/- 0.03 and 0.24 +/- 0.02; Rox: 0.31 +/- 0.02 and 0.20 +/- 0.02 mmol.min, respectively, P ¡ 0.01). This resulted in greater plasma FFA and total fat oxidation rates in the trained versus sedentary subjects (P ¡ 0.001). Muscle- and/or lipoprotein-derived TG use contributed 10 +/- 2 and 11 +/- 3% in the trained and control groups, respectively (NS). No significant net changes in muscle fiber lipid content were observed.nnCONCLUSIONS: Older, endurance-trained males oxidize more fat during moderate-intensity exercise than do sedentary controls. This greater total fat oxidation rate is attributed to a higher plasma FFA release, uptake, and oxidation rate. In contrast, intramyocellular triacylglycerol does not seem to represent a major substrate source during 1 h of moderate-intensity exercise in older trained or sedentary men.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17626892,

title = {Exercise Training Improves Glycemic Control in Long-Standing Insulin-Treated Type 2 Diabetic Patients},

author = {Henk M De Feyter and Stephan F Praet and Nicole M Broek and Harm Kuipers and Coen D Stehouwer and Klaas Nicolay and Jeanine J Prompers and Luc J C Loon},

doi = {10.2337/dc07-0183},

issn = {1935-5548},

year  = {2007},

date = {2007-10-01},

journal = {Diabetes Care},

volume = {30},

number = {10},

pages = {2511–2513},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17656625,

title = {Optimizing the Therapeutic Benefits of Exercise in Type 2 Diabetes},

author = {Stephan F E Praet and Luc J C Loon},

doi = {10.1152/japplphysiol.00566.2007},

issn = {8750-7587},

year  = {2007},

date = {2007-10-01},

journal = {Journal of applied physiology (Bethesda, Md. : 1985)},

volume = {103},

number = {4},

pages = {1113–1120},

abstract = {Other than diet and medication, exercise is considered one of the three cornerstones of good diabetes treatment. Nevertheless, current clinical guidelines on Type 2 diabetes provide no detailed information on the modalities of effective exercise intervention in the treatment of Type 2 diabetes. Based on a review of currently available literature, exercise modalities are being identified to maximize the benefits of exercise intervention in the treatment of different Type 2 diabetes subpopulations. Both endurance and resistance types of exercise have equal therapeutic strength to improve metabolic control in patients with Type 2 diabetes. When applying endurance-type exercise, energy expenditure should be equivalent to approximately 1.7-2.1 MJ/exercise bout on 3 but preferably 5 days/wk. In sarcopenic or severely deconditioned patients with Type 2 diabetes, focus should lie on the implementation of resistance-type exercise to attenuate and/or reverse the decline in skeletal muscle mass and strength. Before choosing the most appropriate exercise modalities, the patient's disease stage should be well characterized, and an ECG-stress test should be considered. Based on baseline aerobic fitness, level of co-morbidities, body composition, and muscle strength, patients should be provided with an individually tailored exercise intervention program to optimize therapeutic value. A multidisciplinary individualized approach and continued exercise training under personal supervision is essential to enhance compliance and allow long-term health benefits of an exercise intervention program.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17609259,

title = {Coingestion of Carbohydrate with Protein Does Not Further Augment Postexercise Muscle Protein Synthesis},

author = {René Koopman and Milou Beelen and Trent Stellingwerff and Bart Pennings and Wim H M Saris and Arie K Kies and Harm Kuipers and Luc J C Loon},

doi = {10.1152/ajpendo.00135.2007},

issn = {0193-1849},

year  = {2007},

date = {2007-09-01},

journal = {American journal of physiology. Endocrinology and metabolism},

volume = {293},

number = {3},

pages = {E833–E842},

abstract = {The present study was designed to assess the impact of coingestion of various amounts of carbohydrate combined with an ample amount of protein intake on postexercise muscle protein synthesis rates. Ten healthy, fit men (20 +/- 0.3 yr) were randomly assigned to three crossover experiments. After 60 min of resistance exercise, subjects consumed 0.3 g x kg(-1) x h(-1) protein hydrolysate with 0, 0.15, or 0.6 g x kg(-1) x h(-1) carbohydrate during a 6-h recovery period (PRO, PRO + LCHO, and PRO + HCHO, respectively). Primed, continuous infusions with L-[ring-(13)C(6)]phenylalanine, L-[ring-(2)H(2)]tyrosine, and [6,6-(2)H(2)]glucose were applied, and blood and muscle samples were collected to assess whole body protein turnover and glucose kinetics as well as protein fractional synthesis rate (FSR) in the vastus lateralis muscle over 6 h of postexercise recovery. Plasma insulin responses were significantly greater in PRO + HCHO compared with PRO + LCHO and PRO (18.4 +/- 2.9 vs. 3.7 +/- 0.5 and 1.5 +/- 0.2 U.6 h(-1) x l(-1), respectively, P ¡ 0.001). Plasma glucose rate of appearance (R(a)) and disappearance (R(d)) increased over time in PRO + HCHO and PRO + LCHO, but not in PRO. Plasma glucose R(a) and R(d) were substantially greater in PRO + HCHO vs. both PRO and PRO + LCHO (P ¡ 0.01). Whole body protein breakdown, synthesis, and oxidation rates, as well as whole body protein balance, did not differ between experiments. Mixed muscle protein FSR did not differ between treatments and averaged 0.10 +/- 0.01, 0.10 +/- 0.01, and 0.11 +/- 0.01%/h in the PRO, PRO + LCHO, and PRO + HCHO experiments, respectively. In conclusion, coingestion of carbohydrate during recovery does not further stimulate postexercise muscle protein synthesis when ample protein is ingested.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17634259,

title = {Protein Ingestion Further Augments S6K1 Phosphorylation in Skeletal Muscle Following Resistance Type Exercise in Males},

author = {René Koopman and Bart Pennings and Antoine H G Zorenc and Luc J C Loon},

doi = {10.1093/jn/137.8.1880},

issn = {0022-3166},

year  = {2007},

date = {2007-08-01},

journal = {The Journal of nutrition},

volume = {137},

number = {8},

pages = {1880–1886},

abstract = {Our objective was to determine the impact of carbohydrate and/or protein ingestion before and after exercise on ribosomal protein S6 kinase (S6K1) and S6 phosphorylation status in human skeletal muscle tissue. Seven healthy, untrained men (22.5 +/- 0.9 y) were randomly assigned to 2 cross-over experiments. Before, immediately after, and 1 h after a single bout of resistance exercise, subjects consumed 0.3 g x kg(-1) carbohydrate with or without 0.3 g x kg(-1) protein hydrolysate (CHO+PRO and CHO, respectively). Muscle biopsies were taken before and immediately after exercise and after 1 and 4 h of postexercise recovery to determine 4E-BP1, S6K1 (both T(421)/S(424) and T(389)), and S6 phosphorylation status. Following resistance exercise, 4E-BP1 phosphorylation was reduced to a greater extent in the CHO treatment (-48 +/- 7%) than in the CHO+PRO treatment (-15 +/- 14%, P ¡ 0.01). During recovery, 4E-BP1 phosphorylation increased in both experiments (P ¡ 0.01), and tended to be higher in the CHO+PRO test (P = 0.08). S6K1 phosphorylation at T(421)/S(424) substantially increased following exercise and remained elevated during recovery with no differences between treatments. In contrast to the CHO treatment (-4 +/- 2%), S6K1 phosphorylation at T(389) was higher following exercise in the CHO+PRO treatment only (+78 +/- 2%, P ¡ 0.01). During recovery, S6K1 phosphorylation at T(389) remained higher in CHO+PRO than in CHO (P ¡ 0.05). S6 phosphorylation was substantially higher following exercise in the CHO+PRO (1.69 +/- 0.35) than in the CHO experiment (0.45 +/- 0.07, P ¡ 0.01) and remained elevated during recovery (P ¡ 0.05). We conclude that the availability of dietary protein further enhances phosphorylation of S6K1 during recovery from resistance type exercise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18577770,

title = {Protein and Protein Hydrolysates in Sports Nutrition},

author = {Luc J C Loon and Arie K Kies and Wim H M Saris},

doi = {10.1123/ijsnem.17.s1.s1},

issn = {1543-2742},

year  = {2007},

date = {2007-08-01},

journal = {International journal of sport nutrition and exercise metabolism},

volume = {17 Suppl},

pages = {S1–S4},

abstract = {With the increasing knowledge about the role of nutrition in increasing exercise performance, it has become clear over the last 2 decades that amino acids, protein, and protein hydrolysates can play an important role. Most of the attention has been focused on their effects at a muscular level. As these nutrients are ingested, however, it also means that gastrointestinal digestibility and absorption can modulate their efficacy significantly. Therefore, discussing the role of amino acids, protein, and protein hydrolysates in sports nutrition entails holding a discussion on all levels of the metabolic route. On May 28-29, 2007, a small group of researchers active in the field of exercise science and protein metabolism presented an overview of the different aspects of the application of protein and protein hydrolysates in sports nutrition. In addition, they were asked to share their opinions on the future progress in their fields of research. In this overview, an introduction to the workshop and a short summary of its outcome is provided.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid18577771,

title = {Application of Protein or Protein Hydrolysates to Improve Postexercise Recovery},

author = {Luc J C Loon},

doi = {10.1123/ijsnem.17.s1.s104},

issn = {1543-2742},

year  = {2007},

date = {2007-08-01},

journal = {International journal of sport nutrition and exercise metabolism},

volume = {17 Suppl},

pages = {S104–S117},

abstract = {Protein, protein hydrolysates, and amino acids have become popular ingredients in sports nutrition. The use of protein, protein hydrolysates, and amino acid mixtures has multiple applications when aiming to improve postexercise recovery. After exhaustive endurance-type exercise, muscle glycogen repletion is the most important factor determining the time needed to recover. Coingestion of relatively small amounts of protein and/or amino acids with carbohydrate can be used to augment postprandial insulin secretion and accelerate muscle glycogen synthesis rates. Furthermore, it has been well established that ingesting protein, protein hydrolysates, and amino acid can stimulate protein synthesis and inhibit protein breakdown and, as such, improve net muscle protein balance after resistance- or endurance-type exercise. The latter has been suggested to lead to a more effective adaptive response to each successive exercise bout. To augment net muscle protein accretion, athletes involved in resistance-type exercise generally ingest both protein and carbohydrate during postexercise recovery. However, carbohydrate ingestion after resistance-type exercise does not seem to be warranted to further stimulate muscle protein synthesis or improve whole-body protein balance when ample protein has already been ingested. Because resistance-type exercise is also associated with a substantial reduction in muscle glycogen content, it would be preferred to coingest some carbohydrate when aiming to accelerate glycogen repletion. More research is warranted to assess the impact of ingesting different proteins, protein hydrolysates, and/or amino acids on muscle protein accretion after exercise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mauricem.a.l.pelsers2007,

title = {Skeletal Muscle Fatty Acid Transporter Protein Expression in Type 2 Diabetes Patients Compared with Overweight, Sedentary Men and Age-Matched, Endurance-Trained Cyclists.},

author = {Maurice M. A. L. Pelsers and Maurice M. A. L. Pelsers and Kostas Tsintzas and Kostas Tsintzas and Hanneke Boon and Hanneke Boon and Kirsty Jewell and K. Jewell and Luke Norton and Luke Norton and Joost J. F. P. Luiken and Joost J. F. P. Luiken and Jan F. C. Glatz and Jan F. C. Glatz and Luc J. C. Loon and Luc J. C. Loon and L. J. C. Loon},

doi = {10.1111/j.1748-1716.2007.01698.x},

year  = {2007},

date = {2007-07-01},

journal = {Acta Physiologica},

volume = {190},

number = {3},

pages = {209–219},

abstract = {Aim: Membrane fatty acid transporters can modulate the balance between fatty acid uptake and subsequent storage and/or oxidation in muscle tissue. As such, skeletal muscle fatty acid transporter protein expression could play an important role in the etiology of insulin resistance and/or type 2 diabetes. Methods: In the present study, fatty acid translocase (FAT/CD36), plasma membrane-bound fatty acid-binding protein (FABPpm) and fatty acid transport protein 1 (FATP1) mRNA and protein expression were assessed in muscle tissue obtained from 10 sedentary, overweight type 2 diabetes patients (60±2years), 10 sedentary, weight-matched normoglycemic controls (60±2years) and 10 age-matched, endurance trained cyclists (57±1years). Results: Both FAT/CD36 and FATP1 mRNA and protein expression did not differ between groups. In contrast, FABPpm mRNA and protein expression were approx. 30–40% higher in the trained men compared with the diabetes patients (P$<$0.01) and sedentary controls (P$<$0.05). Conclusions: Skeletal muscle FAT/CD36, FABPpm and FATP1 mRNA and protein expression are not up- or downregulated in a sedentary and/or insulin resistant state. In contrast, FABPpm expression is upregulated in the endurance trained state and likely instrumental to allow greater fatty acid oxidation rates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17333244,

title = {Carbohydrate Supplementation during Prolonged Cycling Exercise Spares Muscle Glycogen but Does Not Affect Intramyocellular Lipid Use},

author = {Trent Stellingwerff and Hanneke Boon and Annemie P Gijsen and Jos H C H Stegen and Harm Kuipers and Luc J C Loon},

doi = {10.1007/s00424-007-0236-0},

issn = {0031-6768},

year  = {2007},

date = {2007-07-01},

journal = {Pflügers Archiv : European journal of physiology},

volume = {454},

number = {4},

pages = {635–647},

abstract = {Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 +/- 4% of maximal O(2) uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg(-1) h(-1)) or without (CON placebo trial; water only). Continuous infusions with [U-(13)C] palmitate and [6,6-(2)H(2)] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (R (a)) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 +/- 19 and 57 +/- 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA R (a) and subsequent plasma FFA concentrations were lower, resulting in a 34 +/- 12% reduction in plasma FFA oxidation rates during exercise (P ¡ 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 +/- 21 and 78 +/- 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17492425,

title = {The Effect of Moderate Alcohol Consumption on Adiponectin Oligomers and Muscle Oxidative Capacity: A Human Intervention Study},

author = {J W J Beulens and L J C Loon and F J Kok and M Pelsers and T Bobbert and J Spranger and A Helander and H F J Hendriks},

doi = {10.1007/s00125-007-0699-8},

issn = {0012-186X},

year  = {2007},

date = {2007-07-01},

journal = {Diabetologia},

volume = {50},

number = {7},

pages = {1388–1392},

abstract = {AIMS/HYPOTHESIS: The aim of this study was to investigate whether moderate alcohol consumption increases plasma high molecular weight (HMW) adiponectin and/or muscle oxidative capacity.nnMATERIALS AND METHODS: Eleven lean (BMI 18-25 kg/m(2)) and eight overweight (BMI ¿or=27 kg/m(2)) men consumed 100 ml whisky ( approximately 32 g alcohol) or water daily for 4 weeks in a randomised, controlled, crossover trial. After each treatment period, muscle biopsies and fasting blood samples were collected.nnRESULTS: Adiponectin concentrations increased (p ¡ 0.001) by 12.5% after 4 weeks of moderate alcohol consumption. Moderate alcohol consumption tended to increase HMW adiponectin by 57% (p = 0.07) and medium molecular weight adiponectin by 12.5% (p = 0.07), but not low molecular weight (LMW) adiponectin. Skeletal muscle citrate synthase, cytochrome c oxidase and beta-3-hydroxyacyl coenzyme A dehydrogenase (beta-HAD) activity were not changed after moderate alcohol consumption, but an interaction between alcohol consumption and BMI was observed for cytochrome c oxidase (p = 0.072) and citrate synthase (p = 0.102) activity. Among lean men, moderate alcohol consumption tended to increase cytochrome c oxidase (p = 0.08) and citrate synthase activity (p = 0.12) by 23 and 26%, respectively, but not among overweight men. In particular, plasma HMW adiponectin correlated positively with activities of skeletal muscle citrate synthase (r = 0.64},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17299080,

title = {Significant Intramyocellular Lipid Use during Prolonged Cycling in Endurance-Trained Males as Assessed by Three Different Methodologies},

author = {Trent Stellingwerff and Hanneke Boon and Richard A M Jonkers and Joan M Senden and Lawrence L Spriet and René Koopman and Luc J C Loon},

doi = {10.1152/ajpendo.00678.2006},

issn = {0193-1849},

year  = {2007},

date = {2007-06-01},

journal = {American journal of physiology. Endocrinology and metabolism},

volume = {292},

number = {6},

pages = {E1715–E1723},

abstract = {Intramyocellular triacylglycerol (IMTG) has been suggested to represent an important substrate source during exercise. In the present study, IMTG utilization during exercise is assessed through the use of various methodologies. In addition, we identified differences in the use of intramyocellular lipids deposited in the immediate subsarcolemmal (SS) area and those stored in the more central region of the fiber. Contemporary stable isotope technology was applied in combination with muscle tissue sampling before and immediately after 3 h of moderate-intensity cycling exercise (62 +/- 2% Vo(2 max)) in eight well-trained male cyclists. Continuous infusions with [U-13C]palmitate and [6,6-(2)H2]glucose were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate whole body IMTG and glycogen use. Both immunohistochemical analyses of oil red O (ORO)-stained muscle cross sections and biochemical triacylglycerol (TG) extraction were performed to assess muscle lipid content. During exercise, plasma FFA, muscle (and/or lipoprotein)-derived TG, plasma glucose, and muscle glycogen oxidation contributed 24 +/- 2, 22 +/- 3, 11 +/- 1, and 43 +/- 3% to total energy expenditure, respectively. In accordance, a significant net decline in muscle lipid content was observed following exercise as assessed by ORO staining (67 +/- 8%) and biochemical TG extraction (49 +/- 8%), and a positive correlation was observed between methods (r = 0.56; P ¡ 0.05). Lipid depots located in the SS area were utilized to a greater extent than the more centrally located depots. This is the first study to show significant use of IMTG as a substrate source during exercise in healthy males via the concurrent implementation of three major methodologies. In addition, this study shows differences in resting subcellular intramyocellular lipid deposit distribution and in the subsequent net use of these deposits during exercise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17510698,

title = {Responses to Acute Exercise in Type 2 Diabetes, with an Emphasis on Metabolism and Interaction with Oral Hypoglycemic Agents and Food Intake},

author = {Henrik Galbo and Lillan Tobin and Luc J C Loon},

doi = {10.1139/H07-029},

issn = {1715-5312},

year  = {2007},

date = {2007-06-01},

journal = {Applied physiology, nutrition, and metabolism = Physiologie appliquée, nutrition et métabolisme},

volume = {32},

number = {3},

pages = {567–575},

abstract = {In people with type 1 diabetes mellitis (DM), insulin administration, food intake, and exercise have to be carefully matched to avoid either hypo- or hyperglycemia. People with type 2 DM have some insulin secretion, which changes with needs. Accordingly, during exercise, these people do not run the same metabolic risks as people with type 1 DM. However, a contraction-mediated increase in glucose clearance in muscle is intact in type 2 DM. Therefore, in the postabsorptive state in diet-treated type 2 DM, a marked reduction in hyperglycemia can occur during prolonged moderate exercise. Sulfonylurea drugs augment the rate of decline in plasma glucose, because stimulation of insulin secretion reduces hepatic glucose production. After abstention from sulfonylurea for 5 days, the rate of decrease in plasma glucose with exercise is also enhanced, but from a higher glucose level. In the postabsorptive state, brief vigourous exercise elicits an increase in plasma glucose concentration, reflecting an exaggerated counterregulatory hormone response and glucose production. Moreover, insulin sensitivity is reduced in the early postexercise period. In the postprandial state, both prolonged moderate exercise and intermittent high-intensity exercise markedly decrease meal-induced increases in glucose, insulin, and C-peptide concentrations, whereas glucose appearance in plasma is unchanged. When exercise bouts are isocaloric, responses are identical, indicating that overall energy expenditure, and not peak exercise intensity, is the major determinant of exercise-induced changes in overall glucose homeostasis and insulin secretion in type 2 DM. Neither prolonged moderate nor intermittent high-intensity exercise performed in the postprandial state influences glucose or insulin responses to a subsequent meal. Finally, in people with type 2 DM, after a high-fat meal, prolonged moderate exercise reduces the exaggerated increases in plasma concentrations of triglycerides contained in chylomicrons and very low-density lipoproteins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{trentstellingwerff2007,

title = {Carbohydrate Supplementation During Prolonged Cycling Exercise Spares Muscle Glycogen But Does Not Affect Intramyocellular Lipid Use.: 601},

author = {Trent Stellingwerff and Hanneke Boon and Annemie P. Gijsen and Jos H. C. H. Stegen and H. Kuipers and Luc J. C. Loon},

doi = {10.1249/01.mss.0000272960.60101.aa},

year  = {2007},

date = {2007-05-01},

journal = {Medicine and Science in Sports and Exercise},

volume = {39},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17186295,

title = {Reduced Plasma Free Fatty Acid Availability during Exercise: Effect on Gene Expression},

author = {Rebecca J Tunstall and Andrew J McAinch and Mark Hargreaves and Luc J C Loon and David Cameron-Smith},

doi = {10.1007/s00421-006-0376-5},

issn = {1439-6319},

year  = {2007},

date = {2007-03-01},

journal = {European journal of applied physiology},

volume = {99},

number = {5},

pages = {485–493},

abstract = {Endurance exercise transiently increases the mRNA of key regulatory proteins involved in skeletal muscle metabolism. During prolonged exercise and subsequent recovery, circulating plasma fatty acid (FA) concentrations are elevated. The present study therefore aimed to determine the sensitivity of key metabolic genes to FA exposure, assessed in vitro using L6 myocytes and secondly, to measure the expression of these same set of genes in vivo, following a single exercise bout when the post-exercise rise in plasma FA is abolished by acipimox. Initial studies using L6 myotubes demonstrated dose responsive sensitivity for both PDK4 and PGC-1alpha mRNA to acute FA exposure in vitro. Nine active males performed two trials consisting of 2 h exercise, followed by 2 h of recovery. In one trial, plasma FA availability was reduced by the administration of acipimox (LFA), a pharmacological inhibitor of adipose tissue lipolysis, and in the second trial a placebo was provided (CON). During the exercise bout and during recovery, the rise in plasma FA and glycerol was abolished by acipimox treatment. Following exercise the mRNA abundance of PDK4 and PGC-1alpha were elevated and unaffected by either acipimox or placebo. Further analysis of skeletal muscle gene expression demonstrated that the CPT I gene was suppressed in both trials, whilst UCP-3 gene was only modestly regulated by exercise alone. Acipimox ingestion did not alter the response for both CPT I and UCP-3. Thus, this study demonstrates that the normal increase in circulating concentrations of FA during the later stages of exercise and subsequent recovery is not required to induce skeletal muscle mRNA expression of several proteins involved in regulating substrate metabolism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{praet2007,

title = {31P MR Spectroscopy and in Vitro Markers of Oxidative Capacity in Type 2 Diabetes Patients.},

author = {Stephan F. E. Praet and H. M. M. L. Feyter and Richard A. M. Jonkers and Klaas Nicolay and C. Pul and Harm Kuipers and Luc J. C. Loon and Jeanine J. Prompers},

doi = {10.1007/s10334-006-0060-0},

year  = {2007},

date = {2007-01-01},

journal = {Magnetic Resonance Materials in Physics Biology and Medicine},

volume = {19},

number = {6},

pages = {321–331},

abstract = {Background: Skeletal muscle mitochondrial function in type 2 diabetes (T2D) is currently being studied intensively. In vivo 31P magnetic resonance spectroscopy (31P MRS) is a noninvasive tool used to measure mitochondrial respiratory function (MIFU) in skeletal muscle tissue. However, microvascular co-morbidity in long-standing T2D can interfere with the 31P MRS methodology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16926381,

title = {Satellite Cell Content Is Specifically Reduced in Type II Skeletal Muscle Fibers in the Elderly},

author = {Lex B Verdijk and René Koopman and Gert Schaart and Kenneth Meijer and Hans H C M Savelberg and Luc J C Loon},

doi = {10.1152/ajpendo.00278.2006},

issn = {0193-1849},

year  = {2007},

date = {2007-01-01},

journal = {American journal of physiology. Endocrinology and metabolism},

volume = {292},

number = {1},

pages = {E151–E157},

abstract = {Satellite cells (SC) are essential for skeletal muscle growth and repair. Because sarcopenia is associated with type II muscle fiber atrophy, we hypothesized that SC content is specifically reduced in the type II fibers in the elderly. A total of eight elderly (E; 76 +/- 1 yr) and eight young (Y; 20 +/- 1 yr) healthy males were selected. Muscle biopsies were collected from the vastus lateralis in both legs. ATPase staining and a pax7-antibody were used to determine fiber type-specific SC content (i.e., pax7-positive SC) on serial muscle cross sections. In contrast to the type I fibers, the proportion and mean cross-sectional area of the type II fibers were substantially reduced in E vs. Y. The number of SC per type I fiber was similar in E and Y. However, the number of SC per type II fiber was substantially lower in E vs. Y (0.044 +/- 0.003 vs. 0.080 +/- 0.007; P ¡ 0.01). In addition, in the type II fibers, the number of SC relative to the total number of nuclei and the number of SC per fiber area were also significantly lower in E. This study is the first to show type II fiber atrophy in the elderly to be associated with a fiber type-specific decline in SC content. The latter is evident when SC content is expressed per fiber or per fiber area. The decline in SC content might be an important factor in the etiology of type II muscle fiber atrophy, which accompanies the loss of skeletal muscle with aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17062764,

title = {High-Fat/Low-Carbohydrate Diet Reduces Insulin-Stimulated Carbohydrate Oxidation but Stimulates Nonoxidative Glucose Disposal in Humans: An Important Role for Skeletal Muscle Pyruvate Dehydrogenase Kinase 4},

author = {K Chokkalingam and K Jewell and L Norton and J Littlewood and L J C Loon and P Mansell and I A Macdonald and K Tsintzas},

doi = {10.1210/jc.2006-1592},

issn = {0021-972X},

year  = {2007},

date = {2007-01-01},

journal = {The Journal of clinical endocrinology and metabolism},

volume = {92},

number = {1},

pages = {284–292},

abstract = {AIM: The aim of this report was to study the effect of high-fat (HF)/low-carbohydrate (CHO) diet on regulation of substrate metabolism in humans.nnMETHODS: Ten healthy men consumed either a HF (75% energy as fat) or control (35%) diet for 6 d in random order. On d 7, blood glucose disappearance rate (Rd) was determined before and during a hyperinsulinemic euglycemic clamp. Substrate oxidation was determined by indirect calorimetry. Muscle biopsies were obtained prediet, postdiet, and postclamps.nnRESULTS: Rd was similar under basal conditions but slightly elevated (approximately 10%, P ¡ 0.05) during the last 30 min of the clamp after the HF diet. HF diet reduced CHO oxidation under basal (by approximately 40%, P ¡ 0.05) and clamp conditions (by approximately 20%, P ¡ 0.05), increased insulin-mediated whole-body nonoxidative glucose disposal (by 30%, P ¡ 0.05) and muscle glycogen storage (by approximately 25%, P ¡ 0.05). Muscle pyruvate dehydrogenase complex activity was blunted under basal and clamp conditions after HF compared with control (P ¡ 0.05) and was accompanied by an approximately 2-fold increase (P ¡ 0.05) in pyruvate dehydrogenase kinase 4 (PDK4) mRNA and protein expression.nnCONCLUSION: Short-term HF/low-CHO dietary intake did not induce whole-body insulin resistance, but caused a shift in im glucose metabolism from oxidation to glycogen storage. Insulin-stimulated CHO oxidation and muscle pyruvate dehydrogenase complex activity were blunted after the HF diet. Up-regulation of muscle PDK4 expression was an early molecular adaptation to these changes, and we showed for the first time in healthy humans, unlike insulin-resistant individuals, that insulin can suppress PDK4 but not PDK2 gene expression in skeletal muscle.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17131144,

title = {Substrate Source Utilisation in Long-Term Diagnosed Type 2 Diabetes Patients at Rest, and during Exercise and Subsequent Recovery},

author = {H Boon and E E Blaak and W H M Saris and H A Keizer and A J M Wagenmakers and L J C Loon},

doi = {10.1007/s00125-006-0482-2},

issn = {0012-186X},

year  = {2007},

date = {2007-01-01},

journal = {Diabetologia},

volume = {50},

number = {1},

pages = {103–112},

abstract = {AIMS/HYPOTHESIS: Disturbances in substrate source metabolism and, more particularly, in fatty acid metabolism, play an important role in the aetiology and progression of type 2 diabetes. However, data on substrate source utilisation in type 2 diabetes are inconclusive.nnMETHODS: [U-(13)C]palmitate and [6,6-(2)H(2)]glucose tracers were used to assess plasma NEFA and glucose oxidation rates and to estimate the use of muscle- and/or lipoprotein-derived triacylglycerol and muscle glycogen. Subjects were ten male patients who had a long-term (7 +/- 1 years) diagnosis of type 2 diabetes and were overweight, and ten matched healthy, male control subjects. Muscle biopsy samples were collected before and after exercise to assess muscle fibre type-specific intramyocellular lipid and glycogen content.nnRESULTS: At rest and during exercise, the diabetes patients had greater values than the controls for palmitate rate of appearance (Ra) (rest, 2.46 +/- 0.18 and 1.85 +/- 0.20 respectively; exercise, 3.71 +/- 0.36 and 2.84 +/- 0.20 micromol kg(-1) min(-1)) and rate of disappearance (Rd) (rest, 2.45 +/- 0.18 and 1.83 +/- 0.20; exercise, 3.64 +/- 0.35 and 2.80 +/- 0.20 micromol kg(-1) min(-1) respectively). This was accompanied by significantly higher fat oxidation rates at rest and during recovery in the diabetes patients (rest, 0.11 +/- 0.01 in diabetes patients and 0.09 +/- 0.01 in controls; recovery, 0.13 +/- 0.01 and 0.11 +/- 0.01 g/min respectively), despite significantly greater plasma glucose Ra, Rd and circulating plasma glucose concentrations. Furthermore, exercise significantly lowered plasma glucose concentrations in the diabetes patients, as a result of increased blood glucose disposal.nnCONCLUSION: This study demonstrates that substrate source utilisation in long-term-diagnosed type 2 diabetes patients, in whom compensatory hyperinsulinaemia is no longer present, shifts towards an increase in whole-body fat oxidation rate and is accompanied by disturbances in fat and carbohydrate handling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17190534,

title = {The Effects of Exercise Training on Fat-Mass Loss in Obese Patients during Energy Intake Restriction},

author = {Dominique Hansen and Paul Dendale and Jan Berger and Luc J C Loon and Romain Meeusen},

doi = {10.2165/00007256-200737010-00003},

issn = {0112-1642},

year  = {2007},

date = {2007-01-01},

journal = {Sports medicine (Auckland, N.Z.)},

volume = {37},

number = {1},

pages = {31–46},

abstract = {Dietary restriction combined with endurance exercise training represents an effective strategy to promote weight loss and reduce fat mass in obese patients. Exercise programmes without dietary restriction are less efficient. However, addition of exercise to a dietary restriction programme does not induce a greater fat-mass loss than dietary restriction alone. The latter is likely attributed to a compensatory reduction in daily physical activity following the implementation of exercise training. Nonetheless, inclusion of an exercise training programme is important to prevent a decrease in fat-free mass, increase relative visceral fat-mass loss, improve dietary compliance and eventually maintain long-term weight control. Obese male patients with the highest fat mass are most likely to lose the largest amount of fat mass in such lifestyle intervention programmes. Influences of training modalities during energy intake restriction on fat-mass loss are reviewed. The relationship between total energy expenditure during exercise training and overall fat-mass loss has been firmly established. The amount of training forms a more important predictor of fat-mass loss than training intensity. The sort of exercise (e.g. walking, cycling, swimming) plays another important predictor of fat-mass loss in intervention programmes. The implementation of resistance training in such programmes does not augment fat-mass loss but improves body composition by increasing fat-free mass. Further studies are needed to define the optimal interventional programme for obese patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17645370,

title = {Thermoregulation during Exercise in the Heat: Strategies for Maintaining Health and Performance},

author = {Daniël Wendt and Luc J C Loon and Wouter D Marken Lichtenbelt},

doi = {10.2165/00007256-200737080-00002},

issn = {0112-1642},

year  = {2007},

date = {2007-01-01},

journal = {Sports medicine (Auckland, N.Z.)},

volume = {37},

number = {8},

pages = {669–682},

abstract = {As a result of the inefficiency of metabolic transfer, ¿75% of the energy that is generated by skeletal muscle substrate oxidation is liberated as heat. During exercise, several powerful physiological mechanisms of heat loss are activated to prevent an excessive rise in body core temperature. However, a hot and humid environment can significantly add to the challenge that physical exercise imposes on the human thermoregulatory system, as heat exchange between body and environment is substantially impaired under these conditions. This can lead to serious performance decrements and an increased risk of developing heat illness. Fortunately, there are a number of strategies that athletes can use to prevent and/or reduce the dangers that are associated with exercise in the heat. In this regard, heat acclimatisation and nutritional intervention seem to be most effective. During heat acclimatisation, the temperature thresholds for both cutaneous vasodilation and the onset of sweating are lowered, which, in combination with plasma volume expansion, improve cardiovascular stability. Effective nutritional interventions include the optimisation of hydration status by the use of fluid replacement beverages. The latter should contain moderate amounts of glucose and sodium, which improve both water absorption and retention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17887813,

title = {Nutritional Interventions to Promote Post-Exercise Muscle Protein Synthesis},

author = {René Koopman and Wim H M Saris and Anton J M Wagenmakers and Luc J C Loon},

doi = {10.2165/00007256-200737100-00005},

issn = {0112-1642},

year  = {2007},

date = {2007-01-01},

journal = {Sports medicine (Auckland, N.Z.)},

volume = {37},

number = {10},

pages = {895–906},

abstract = {Resistance exercise is a powerful stimulus to augment muscle protein anabolism, as it can improve the balance between muscle protein synthesis and breakdown. However, the intake of food during post-exercise recovery is necessary for hypertrophy to occur. Therefore, athletes need to ingest protein following exercise to attain a positive protein balance and maximise their skeletal muscle adaptive response. The interaction between exercise and nutrition is not only important for athletes, but is also of important clinical relevance in the elderly. Exercise interventions combined with specific nutritional modulation provide an effective strategy to counteract or reduce the loss of skeletal muscle mass with aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17130211,

title = {Protein Hydrolysate/Leucine Co-Ingestion Reduces the Prevalence of Hyperglycemia in Type 2 Diabetic Patients},

author = {Ralph J F Manders and Stephan F E Praet and Ruth C R Meex and René Koopman and André L Roos and Anton J M Wagenmakers and Wim H M Saris and Luc J C Loon},

doi = {10.2337/dc06-1424},

issn = {0149-5992},

year  = {2006},

date = {2006-12-01},

journal = {Diabetes Care},

volume = {29},

number = {12},

pages = {2721–2722},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17146308,

title = {Influence of Acute Exercise on Hyperglycemia in Insulin-Treated Type 2 Diabetes},

author = {Stephan F Praet and Ralph J Manders and A G Lieverse and Harm Kuipers and Coen D Stehouwer and Hans A Keizer and Luc J Loon},

doi = {10.1249/01.mss.0000235352.09061.1d},

issn = {0195-9131},

year  = {2006},

date = {2006-12-01},

journal = {Medicine and science in sports and exercise},

volume = {38},

number = {12},

pages = {2037–2044},

abstract = {INTRODUCTION: The impact of exercise on blood glucose homeostasis has not been assessed in long-standing type 2 diabetes patients receiving exogenous insulin treatment.nnPURPOSE: To study the effects of an acute bout of exercise on the subsequent 24-h blood glucose excursions under free-living conditions in insulin-treated type 2 diabetes patients.nnMETHODS: Eleven male type 2 diabetes patients (59 +/- 2 yr) performed an acute bout of exercise. One day before the exercise bout, a continuous glucose monitoring system (GlucoDay, A. Menarini Diagnostics) was inserted subcutaneously in the periumbilical region. The glucose sensor continuously measured glucose concentrations in the dialysate during a 48-h period.nnRESULTS: The prevalence of hyperglycemic glucose excursions was reduced by 39% during a 24-h period (equivalent to 3 h) after an acute bout of exercise (P ¡ 0.05). Average glucose concentrations 24 h before and after the exercise bout did not differ (NS). Mean dialysate glucose concentrations and the prevalence of hyperglycemic periods correlated strongly with baseline blood HbA1c concentrations (Pearson's R = 0.69, P ¡ 0.05).nnCONCLUSION: An acute bout of exercise effectively reduces the prevalence of hyperglycemia during a 24-h period under free-living conditions in long-standing type 2 diabetes patients on exogenous insulin therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16621642,

title = {Untreated Classical Galactosemia Patient with Mild Phenotype},

author = {Bianca Panis and Jaap A Bakker and Jean-Pierre J E Sels and Leo J M Spaapen and Luc J C Loon and M Estela Rubio-Gozalbo},

doi = {10.1016/j.ymgme.2006.03.002},

issn = {1096-7192},

year  = {2006},

date = {2006-11-01},

journal = {Molecular genetics and metabolism},

volume = {89},

number = {3},

pages = {277–279},

abstract = {Despite life-long galactose restriction, long-term complications generally occur in classical galactosemia. We report an adult male with classical galactosemia (Q188R homozygosity, severely reduced erythrocyte galactose-1-phosphate uridyltransferase activity) who has a surprisingly mild phenotype despite genotype and enzyme activity associated with severe phenotype. Moreover he has a normal galactose intake from the age of 3 years. This case is probably an example of the important role of yet unknown susceptibility and or modifier genes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{renekoopman2006,

title = {Co-Ingestion of Protein and Leucine Stimulates Muscle Protein Synthesis Rates to the Same Extent in Young and Elderly Lean Men},

author = {René Koopman and René Koopman and Lex B. Verdijk and Lex B. Verdijk and Richard T. Jaspers and Ralph J. Manders and Ralph J. F. Manders and Annemie P. Gijsen and Annemie P. Gijsen and M. Gorselink and Marchel Gorselink and Evelien Pijpers and Evelien Pijpers and Anton J. M. Wagenmakers and Anton J. M. Wagenmakers and Luc J. C. Loon and Luc J. C. Loon},

doi = {10.1093/ajcn/84.3.623},

year  = {2006},

date = {2006-09-01},

journal = {The American Journal of Clinical Nutrition},

volume = {84},

number = {3},

pages = {623–632},

abstract = {BACKGROUND: The progressive loss of skeletal muscle mass with aging is attributed to a disruption in the regulation of skeletal muscle protein turnover. OBJECTIVE: We investigated the effects on whole-body protein balance and mixed-muscle protein synthesis rates of the ingestion of carbohydrate with or without protein and free leucine after simulated activities of daily living. DESIGN: Eight elderly (75 +/- 1 y) and 8 young (20 +/- 1 y) lean men were randomly assigned to 2 crossover experiments in which they consumed either carbohydrate (CHO) or carbohydrate plus protein and free leucine (CHO+Pro+Leu) after performing 30 min of standardized activities of daily living. Primed, continuous infusions with L-[ring-13C6]phenylalanine and L-[ring-2H2]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover and the protein fractional synthetic rate in the vastus lateralis muscle over a 6-h period. RESULTS: Whole-body phenylalanine and tyrosine flux were significantly higher in the young than in the elderly men (P $<$ 0.01). Protein balance was negative in the CHO experiment but positive in the CHO+Pro+Leu experiment in both groups. Mixed-muscle protein synthesis rates were significantly greater in the CHO+Pro+Leu than in the CHO experiment in both the young (0.082 +/- 0.005%/h and 0.060 +/- 0.005%/h, respectively; P $<$ 0.01) and the elderly (0.072 +/- 0.006%/h and 0.043 +/- 0.003%/h, respectively; P $<$ 0.01) subjects, with no significant differences between groups. CONCLUSIONS: Co-ingestion of protein and leucine with carbohydrate after activities of daily living improves whole-body protein balance, and the increase in muscle protein synthesis rates is not significantly different between lean young and elderly men.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16613586,

title = {Glycaemic Instability Is an Underestimated Problem in Type II Diabetes},

author = {Stephan F E Praet and Ralph J F Manders and Ruth C R Meex and A G Lieverse and Coen D A Stehouwer and Harm Kuipers and Hans A Keizer and Luc J C Loon},

doi = {10.1042/CS20060041},

issn = {0143-5221},

year  = {2006},

date = {2006-08-01},

journal = {Clinical science (London, England : 1979)},

volume = {111},

number = {2},

pages = {119–126},

abstract = {The aim of the present study was to assess the level of glycaemic control by the measurement of 24 h blood glucose profiles and standard blood analyses under identical nutritional and physical activity conditions in patients with Type II diabetes and healthy normoglycaemic controls. A total of 11 male patients with Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS (continuous subcutaneous glucose-monitoring system) assessment trial under strictly standardized dietary and physical activity conditions. In addition, fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations were measured, and an OGTT (oral glucose tolerance test) was performed to calculate indices of whole-body insulin sensitivity, oral glucose tolerance and/or glycaemic control. In the healthy control group, hyperglycaemia (blood glucose concentration ¿10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h). However, in the patients with Type II diabetes, hyperglycaemia was experienced for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%; P¡0.01 as determined by ANOVA) to the total amount of hyperglycaemia and postprandial glycaemic instability. In the diabetes patients, blood HbA(1c) content correlated well with the duration of hyperglycaemia and the postprandial glucose responses (P¡0.05). In conclusion, CGMS determinations show that standard measurements of glycaemic control underestimate the amount of hyperglycaemia prevalent during real-life conditions in Type II diabetes. Given the macro- and micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an excellent tool to evaluate alternative therapeutic strategies to reduce hyperglycaemic blood glucose excursions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16434552,

title = {Increase in S6K1 Phosphorylation in Human Skeletal Muscle Following Resistance Exercise Occurs Mainly in Type II Muscle Fibers},

author = {René Koopman and Antoine H G Zorenc and Rudy J J Gransier and David Cameron-Smith and Luc J C Loon},

doi = {10.1152/ajpendo.00530.2005},

issn = {0193-1849},

year  = {2006},

date = {2006-06-01},

journal = {American journal of physiology. Endocrinology and metabolism},

volume = {290},

number = {6},

pages = {E1245–E1252},

abstract = {To investigate the in vivo effects of resistance exercise on translational control in human skeletal muscle, we determined the phosphorylation of AMP-activated kinase (AMPK), eukaryotic initiation factor 4E-binding protein (4E-BP1), p70/p85-S6 protein kinase (S6K1), and ribosomal S6 protein (S6). Furthermore, we investigated whether changes in the phosphorylation of S6K1 are muscle fiber type specific. Eight male subjects performed a single high-intensity resistance exercise session. Muscle biopsies were collected before and immediately after exercise and after 30 and 120 min of postexercise recovery. The phosphorylation statuses of AMPK, 4E-BP1, S6K1, and S6 were determined by Western blotting with phospho-specific and pan antibodies. To determine fiber type-specific changes in the phosphorylation status of S6K1, immunofluorescence microscopy was applied. AMPK phosphorylation was increased approximately threefold immediately after resistance exercise, whereas 4E-BP1 phosphorylation was reduced to 27 +/- 6% of preexercise values. Phosphorylation of S6K1 at Thr421/Ser424 was increased 2- to 2.5-fold during recovery but did not induce a significant change in S6 phosphorylation. Phosphorylation of S6K1 was more pronounced in the type II vs. type I muscle fibers. Before exercise, phosphorylated S6K1 was predominantly located in the nuclei. After 2 h of postexercise recovery, phospho-S6K1 was primarily located in the cytosol of type II muscle fibers. We conclude that resistance exercise effectively increases the phosphorylation of S6K1 on Thr421/Ser424, which is not associated with a substantial increase in S6 phosphorylation in a fasted state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16614419,

title = {Co-Ingestion of a Protein Hydrolysate with or without Additional Leucine Effectively Reduces Postprandial Blood Glucose Excursions in Type 2 Diabetic Men},

author = {Ralph J Manders and René Koopman and Wendy E Sluijsmans and Robin Berg and Kees Verbeek and Wim H Saris and Anton J Wagenmakers and Luc J Loon},

doi = {10.1093/jn/136.5.1294},

issn = {0022-3166},

year  = {2006},

date = {2006-05-01},

journal = {The Journal of nutrition},

volume = {136},

number = {5},

pages = {1294–1299},

abstract = {This study examined postprandial plasma insulin and glucose responses after co-ingestion of an insulinotropic protein (Pro) hydrolysate with and without additional free leucine with a single bolus of carbohydrate (Cho). Male patients with long-standing Type 2 diabetes (n = 10) and healthy controls (n = 10) participated in 3 trials in which plasma glucose, insulin, and amino acid responses were determined after the ingestion of beverages of different composition (Cho: 0.7 g/kg carbohydrate, Cho+Pro: 0.7 g/kg carbohydrate with 0.3 g/kg protein hydrolysate, or Cho+Pro+Leu: 0.7 g/kg carbohydrate, 0.3 g/kg protein hydrolysate and 0.1 g/kg free leucine). Plasma insulin responses [expressed as area under the curve (AUC)] were 141 and 204% greater in patients with Type 2 diabetes and 66 and 221% greater in the controls in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P ¡ 0.05). The concomitant plasma glucose responses were 15 and 12% lower in the patients with Type 2 diabetes and 92 and 97% lower in the control group in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P ¡ 0.05). Plasma leucine concentrations correlated with the insulin response in all subjects (r = 0.43, P ¡ 0.001). We conclude that co-ingestion of a protein hydrolysate with or without additional free leucine strongly augments the insulin response after ingestion of a single bolus of carbohydrate, thereby significantly reducing postprandial blood glucose excursions in patients with long-standing Type 2 diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}