All Publications

@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}

}

@article{pmid16549460,

title = {Cinnamon Supplementation Does Not Improve Glycemic Control in Postmenopausal Type 2 Diabetes Patients},

author = {Kristof Vanschoonbeek and Bregje J W Thomassen and Joan M Senden and Will K W H Wodzig and Luc J C Loon},

doi = {10.1093/jn/136.4.977},

issn = {0022-3166},

year  = {2006},

date = {2006-04-01},

journal = {The Journal of nutrition},

volume = {136},

number = {4},

pages = {977–980},

abstract = {In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration. Recently, a human intervention study showed that cinnamon supplementation (1 g/d) strongly reduced fasting blood glucose concentration (30%) and improved the blood lipid profile in patients with type 2 diabetes. The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and/or glucose tolerance and blood lipid profile in patients with type 2 diabetes. Therefore, a total of 25 postmenopausal patients with type 2 diabetes (aged 62.9 +/- 1.5 y, BMI 30.4 +/- 0.9 kg/m2) participated in a 6-wk intervention during which they were supplemented with either cinnamon (Cinnamomum cassia, 1.5 g/d) or a placebo. Before and after 2 and 6 wk of supplementation, arterialized blood samples were obtained and oral glucose tolerance tests were performed. Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined. There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance. The blood lipid profile of fasting subjects did not change after cinnamon supplementation. We conclude that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. More research on the proposed health benefits of cinnamon supplementation is warranted before health claims should be made.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16369816,

title = {Intramyocellular Lipid and Glycogen Content Are Reduced Following Resistance Exercise in Untrained Healthy Males},

author = {René Koopman and Ralph J F Manders and Richard A M Jonkers and Gabby B J Hul and Harm Kuipers and Luc J C Loon},

doi = {10.1007/s00421-005-0118-0},

issn = {1439-6319},

year  = {2006},

date = {2006-03-01},

journal = {European journal of applied physiology},

volume = {96},

number = {5},

pages = {525–534},

abstract = {Resistance exercise has recently been shown to improve whole-body insulin sensitivity in healthy males. Whether this is accompanied by an exercise-induced decline in skeletal muscle glycogen and/or lipid content remains to be established. In the present study, we determined fibre-type-specific changes in skeletal muscle substrate content following a single resistance exercise session. After an overnight fast, eight untrained healthy lean males participated in a approximately 45 min resistance exercise session. Muscle biopsies were collected before, following cessation of exercise, and after 30 and 120 min of post-exercise recovery. Subjects remained fasted throughout the test. Conventional light and (immuno)fluorescence microscopy were applied to assess fibre-type-specific changes in intramyocellular triacylglycerol (IMTG) and glycogen content. A significant 27+/-7% net decline in IMTG content was observed in the type I muscle fibres (P¡0.05), with no net changes in the type IIa and IIx fibres. Muscle glycogen content decreased with 23+/-6, 40+/-7 and 44+/-7% in the type I, IIa and IIx muscle fibres, respectively (P¡0.05). Fibre-type-specific changes in intramyocellular lipid and/or glycogen content correlated well with muscle fibre-type oxidative capacity. During post-exercise recovery, type I muscle fibre lipid content returned to pre-exercise levels within 120 min. No changes in muscle glycogen content were observed during recovery. We conclude that intramyocellular lipid and glycogen stores are readily used during resistance exercise and this is likely associated with the reported increase in whole-body insulin sensitivity following resistance exercise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16155759,

title = {Increased Intramuscular Lipid Storage in the Insulin-Resistant and Endurance-Trained State},

author = {Luc J C Loon and Bret H Goodpaster},

doi = {10.1007/s00424-005-1509-0},

issn = {0031-6768},

year  = {2006},

date = {2006-02-01},

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

volume = {451},

number = {5},

pages = {606–616},

abstract = {Numerous studies have reported a strong correlation between intramuscular triacylglycerol (IMTG) content and insulin resistance. However, the proposed relationship between IMTG accumulation and skeletal muscle insulin resistance is not unambiguous, as trained athletes have been shown to be markedly insulin sensitive despite an elevated IMTG storage. Though the latter has often been attributed to differences in muscle fibre type composition and/or structural characteristics of the intramyocellular lipid deposits, recent studies have failed to provide such evidence. The greater insulin sensitivity despite an elevated IMTG deposition in the endurance-trained state has often been described as a metabolic paradox. However, divergent metabolic events are responsible for the greater IMTG content in the endurance-trained versus insulin-resistant states. The greater IMTG storage in the trained athlete represents an adaptive response to endurance training, allowing a greater contribution of the IMTG pool as a substrate source during exercise. In contrast, elevated IMTG stores in the obese and/or type 2 diabetes patient seem to be secondary to a structural imbalance between plasma free fatty acid availability, fatty acid (FA) storage and oxidation. Therefore, the reported correlation between IMTG content and insulin resistance does not represent a functional relationship, as it is strongly influenced by training status and/or habitual physical activity. It can be argued that the ratio between IMTG content and muscle oxidative capacity represents a more accurate marker of insulin resistance. Interventions to augment mitochondrial density and/or function are likely to improve the balance between FA uptake and oxidation and should be applied to prevent and/or treat insulin resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kaastra2006,

title = {Effects of Increasing Insulin Secretion on Acute Postexercise Blood Glucose Disposal.},

author = {Brechje Kaastra and Richard T. Jaspers and Ralph Manders and Ralph J. F. Manders and Eric Breda and Arie K. Kies and Asker E. Jeukendrup and Hans A. Keizer and Harm Kuipers and Luc J. C. Loon},

doi = {10.1249/01.mss.0000183875.86476.bd},

year  = {2006},

date = {2006-01-01},

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

volume = {38},

number = {2},

pages = {268–275},

abstract = {BACKGROUND: Coingestion of protein and/or free amino acids with carbohydrate has been reported to accelerate postexercise muscle glycogen synthesis due to an increase in the insulin response. PURPOSE: To determine the extent to which the combined ingestion of carbohydrate and a casein protein hydrolysate with or without additional free leucine can increase insulin levels during postexercise recovery in endurance-trained athletes. To determine how this affects whole-body plasma glucose disposal during postexercise recovery. METHODS: Fourteen male athletes (age: 24.3 +/- 0.8 yr; VO2max: 62.9 +/- 1.4 mL.kg.min) were subjected to three randomized crossover trials in which they performed 2 h of exercise (55% Wmax). Thereafter, subjects were studied for 3.5 h during which they ingested carbohydrate (CHO: 0.8 g.kg.h), carbohydrate and a protein hydrolysate (CHO-PRO: 0.8 and 0.4 g.kg.h, respectively), or carbohydrate, a protein hydrolysate, and free leucine (CHO-PRO-LEU: 0.8, 0.4, and 0.1 g.kg.h, respectively) in a double-blind fashion. Continuous infusions with [6,6-H2] glucose were applied to quantify plasma glucose appearance (Ra) and disappearance rates (Rd). RESULTS: Plasma insulin responses were 108 +/- 17 and 190 +/- 33% greater in the CHO-PRO and CHO-PRO-LEU trial, respectively, compared with the CHO-trial (P $<$ 0.01). Plasma glucose responses were lower in the CHO-PRO and CHO-PRO-LEU trial compared with the CHO-trial (35 +/- 5 and 42 +/- 11% lower, respectively; P $<$ 0.01). Plasma glucose Ra and Rd were greater in the CHO versus the CHO-PRO and CHO-PRO-LEU trials (P $<$ 0.05). Glucose Rd represented 100 +/- 0.03% of Ra in all trials. CONCLUSIONS: The combined ingestion of a protein hydrolysate and/or free leucine with carbohydrate (0.8 g.kg.h) substantially augments insulin secretion, but does not affect plasma glucose disposal during the first 3.5 h of postexercise recovery in trained athletes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16463611,

title = {[Insulin Resistance: The Role of Intramuscular Triglyceride and the Importance of Physical Activity]},

author = {R J Timmermans and W H M Saris and L J C Loon},

issn = {0028-2162},

year  = {2006},

date = {2006-01-01},

journal = {Nederlands tijdschrift voor geneeskunde},

volume = {150},

number = {3},

pages = {122–127},

abstract = {In the Netherlands, the prevalence of diabetes is expected to rise from 480,000 to more than 650,000 patients by the year 2020. Numerous studies have reported a strong correlation between elevated plasma-free fatty-acid levels, the accumulation of intramuscular triglyceride (IMTG) and the development of insulin resistance. Traditionally, the Randle cycle was used to explain the mechanism behind fatty acid-induced insulin resistance in skeletal muscle. An alternative explanation is that the increased supply of free fatty acids leads to the accumulation of IMTG and fatty-acid metabolites, which can induce defects in the insulin signalling cascade, causing insulin resistance in skeletal muscle. However, this proposed relationship between elevated IMTG concentrations and skeletal-muscle insulin resistance does not always apply, as trained athletes have been shown to be markedly insulin-sensitive, despite having high levels of stored IMTG. This metabolic paradox is explained by the fact that it is not the size of the IMTG pool but rather the balance between fatty-acid availability, uptake and oxidation, i.e. the low turnover of the IMTG pool, that is instrumental in the development of skeletal-muscle insulin resistance. Physical exercise forms an effective strategy to improve the balance between skeletal-muscle fatty-acid uptake and oxidation and, as such, can prevent the development of skeletal-muscle insulin resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17144879,

title = {Lipid Metabolism, Exercise and Insulin Action},

author = {Arend Bonen and G Lynis Dohm and Luc J C Loon},

doi = {10.1042/bse0420047},

issn = {0071-1365},

year  = {2006},

date = {2006-01-01},

journal = {Essays in biochemistry},

volume = {42},

pages = {47–59},

abstract = {Skeletal muscle constitutes 40% of body mass and takes up 80% of a glucose load. Therefore, impaired glucose removal from the circulation, such as that which occurs in obesity and type 2 diabetes, is attributable in large part to the insulin resistance in muscle. Recent research has shown that fatty acids, derived from adipose tissue, can interfere with insulin signalling in muscle. Hence, insulin-stimulated GLUT4 translocation to the cell surface is impaired, and therefore, the rate of glucose removal from the circulation into muscle is delayed. The mechanisms provoking lipid-mediated insulin resistance are not completely understood. In sedentary individuals, excess intramyocellular accumulation of triacylglycerols is only modestly associated with insulin resistance. In contrast, endurance athletes, despite accumulating large amounts of intramyocellular triacylglycerols, are highly insulin sensitive. Thus it appears that lipid metabolites, other than triacylglycerols, interfere with insulin signalling. These metabolites, however, are not expected to accumulate in athletic muscles, as endurance training increases the capacity for fatty acid oxidation by muscle. These observations, and others in severely obese individuals and type 2 diabetes patients, suggest that impaired rates of fatty acid oxidation are associated with insulin resistance. In addition, in obesity and type 2 diabetes, the rates of fatty acid transport into muscle are also increased. Thus, excess intracellular lipid metabolite accumulation, which interferes with insulin signalling, can occur as a result of impaired rates of fatty acid oxidation and/or increased rates of fatty acid transport into muscle. Accumulation of excess intramyocellular lipid can be avoided by exercise, which improves the capacity for fatty acid oxidation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {[Optimalization of Training Modalities for Patients with Cardiac Disease and Obesity] – Optimalisatie van Trainingsmodaliteiten Voor Hart- En Obesitaspatiënten},

author = {D. Hansen and P. Dendale and LJC Van Loon and R Meeusen},

url = {https://www.sportengeneeskunde.nl/artikelen/434-optimalisatie-van-trainingsmodaliteiten-voor-hart-en-obesitaspatienten.html},

doi = {10.2174/187152207779802428},

year  = {2006},

date = {2006-00-00},

urldate = {2006-00-00},

journal = {Geneeskunde en Sport},

volume = {39},

number = {4},

pages = {145–54},

abstract = {Evidence is accumulating showing amino acids to play a key regulatory role in numerous metabolic processes. Amino acids, and leucine in particular, can be applied as potent insulin secretagogues. These stimulating properties are not restricted to healthy humans, but are also effective in long-term diagnosed type 2 diabetes patients. Co-ingestion of amino acid/protein with carbohydrate substantially augments endogenous insulin release, accelerates blood glucose disposal, and improves post-prandial glucose homeostasis. Besides their function as precursors for protein synthesis, some amino acids are also able to stimulate protein anabolism in an insulin-independent manner. Branched chain amino acids (BCAA), and leucine in particular, are capable of activating the mRNA translational machinery through the mammalian target of rapamycin (mTOR), which represents an interesting molecular target for the prevention or reduction of elevated muscle proteolysis in uncontrolled type 2 diabetes. Protein and/or specific amino acid supplementation could help to reduce muscle proteolysis and/or to stimulate protein synthesis, leading to an improved muscle protein balance, which augments whole-body blood glucose disposal capacity. Besides the potential benefits of protein and/or amino acid supplementation, there is evidence showing hyperaminoacidemia to impair skeletal muscle insulin signaling. Understanding the mechanisms by which different amino acids can alter metabolic signaling will be of great value for the development of effective nutritional and/or pharmacological interventions to prevent and/or treat insulin resistance and/or type 2 diabetes. Studies investigating the benefits of long-term amino acid and/or protein supplementation in type 2 diabetes patients are warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16096823,

title = {Inhibition of Adipose Tissue Lipolysis Increases Intramuscular Lipid Use in Type 2 Diabetic Patients},

author = {L J C Loon and R J F Manders and R Koopman and B Kaastra and J H C H Stegen and A P Gijsen and W H M Saris and H A Keizer},

doi = {10.1007/s00125-005-1889-x},

issn = {0012-186X},

year  = {2005},

date = {2005-10-01},

journal = {Diabetologia},

volume = {48},

number = {10},

pages = {2097–2107},

abstract = {AIMS/HYPOTHESIS: In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients.nnMATERIALS AND METHODS: We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type.nnRESULTS: Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p¡0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p¡0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p¡0.05).nnCONCLUSIONS/INTERPRETATION: This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15886227,

title = {Inhibition of Adipose Tissue Lipolysis Increases Intramuscular Lipid and Glycogen Use in Vivo in Humans},

author = {Luc J C Loon and Michaela Thomason-Hughes and Dumitru Constantin-Teodosiu and René Koopman and Paul L Greenhaff and D Grahame Hardie and Hans A Keizer and Wim H M Saris and Anton J M Wagenmakers},

doi = {10.1152/ajpendo.00092.2005},

issn = {0193-1849},

year  = {2005},

date = {2005-09-01},

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

volume = {289},

number = {3},

pages = {E482–E493},

abstract = {This study investigates the consequences of inhibition of adipose tissue lipolysis on skeletal muscle substrate use. Ten subjects were studied at rest and during exercise and subsequent recovery under normal, fasting conditions (control trial, CON) and following administration of a nicotinic acid analog (low plasma free fatty acid trial, LFA). Continuous [U-13C]palmitate and [6,6-2H2]glucose infusions were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected to measure 1) fiber type-specific IMTG content; 2) allosteric regulators of hormone-sensitive lipase (HSL), glycogen phosphorylase, and pyruvate dehydrogenase; and 3) the phosphorylation status of HSL at Ser563 and Ser565. Administration of a nicotinic acid analog (acipimox) substantially reduced plasma FFA rate of appearance and subsequent plasma FFA concentrations (P ¡ 0.0001). At rest, this substantially reduced plasma FFA oxidation rates, which was compensated by an increase in the estimated IMTG use (P ¡ 0.05). During exercise, the progressive increase in FFA rate of appearance, uptake, and oxidation was prevented in the LFA trial and matched by greater IMTG and glycogen use. Differential phosphorylation of HSL or relief of its allosteric inhibition by long-chain fatty acyl-CoA could not explain the increase in muscle TG use, but there was evidence to support the contention that regulation may reside at the level of the glucose-fatty acid cycle. This study confirms the hypothesis that plasma FFA availability regulates both intramuscular lipid and glycogen use in vivo in humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid16002803,

title = {Co-Ingestion of a Protein Hydrolysate and Amino Acid Mixture with Carbohydrate Improves Plasma Glucose Disposal in Patients with Type 2 Diabetes},

author = {Ralph J F Manders and Anton J M Wagenmakers and René Koopman and Antoine H G Zorenc and Paul P C A Menheere and Nicolaas C Schaper and Wim H M Saris and Luc J C Loon},

doi = {10.1093/ajcn.82.1.76},

issn = {0002-9165},

year  = {2005},

date = {2005-07-01},

journal = {The American journal of clinical nutrition},

volume = {82},

number = {1},

pages = {76–83},

abstract = {BACKGROUND: Although insulin secretion after carbohydrate ingestion is severely impaired in patients with type 2 diabetes, amino acid and protein co-ingestion can substantially increase plasma insulin responses.nnOBJECTIVE: We investigated insulin responses and the subsequent plasma glucose disposal rates after the ingestion of carbohydrate alone (CHO) or with a protein hydrolysate and amino acid mixture (CHO+PRO) in patients with a long-term diagnosis of type 2 diabetes.nnDESIGN: Ten type 2 diabetic patients [mean (+/-SEM) age: 62 +/- 2 y; body mass index (kg/m(2)): 27 +/- 1] and 9 healthy control subjects (age: 58 +/- 1 y; body mass index: 27 +/- 1) participated in 2 trials in which the plasma insulin response was measured after the ingestion of 0.7 g carbohydrate . kg(-1) . h(-1) with or without 0.35 g . kg(-1) . h(-1) of a mixture that contained a protein hydrolysate, leucine, and phenylalanine. Continuous infusions with [6,6-(2)H(2)]glucose were then given to investigate plasma glucose disposal.nnRESULTS: Plasma insulin responses were higher by 299 +/- 64% and 132 +/- 63% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P ¡ 0.001). The subsequent plasma glucose responses were reduced by 28 +/- 6% and 33 +/- 3% in the CHO+PRO trial than in the CHO trial in the diabetic patients and the matched control subjects, respectively (P ¡ 0.001). The reduced plasma glucose response in the diabetic patients was attributed to a 13 +/- 3% increase in glucose disposal (P ¡ 0.01).nnCONCLUSIONS: The combined ingestion of carbohydrate with a protein hydrolysate and amino acid mixture significantly increases de novo insulin production in patients with a long-term diagnosis of type 2 diabetes. The increased insulin response stimulates plasma glucose disposal and reduces postprandial glucose concentrations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15761746,

title = {A Single Session of Resistance Exercise Enhances Insulin Sensitivity for at Least 24 h in Healthy Men},

author = {René Koopman and Ralph J F Manders and Antoine H G Zorenc and Gabby B J Hul and Harm Kuipers and Hans A Keizer and Luc J C Loon},

doi = {10.1007/s00421-004-1307-y},

issn = {1439-6319},

year  = {2005},

date = {2005-05-01},

journal = {European journal of applied physiology},

volume = {94},

number = {1-2},

pages = {180–187},

abstract = {The aim of the present study was to determine whether a single session of resistance exercise improves whole-body insulin sensitivity in healthy men for up to 24 h. Twelve male subjects (23 +/- 1 years) were studied over a period of 4 days during which they consumed a standardized diet, providing 0.16 +/- 0.01 MJ.kg(-1).day(-1) containing 15 +/- 0.1 energy% (En%) protein, 29 +/ -0.1 En% fat and 55 +/- 0.3 En% carbohydrate. Insulin sensitivity was determined 24 h before and 24 h after a single resistance exercise session (8 sets of 10 repetitions at 75% of 1 repetition maximum for two leg exercise tasks) using an intravenous insulin tolerance test. Insulin sensitivity index was calculated by the decline in arterial blood glucose concentration following intravenous administration of a single bolus of human insulin (0.075 IU.kg(-1) fat free mass). Basal glucose and insulin concentrations were not changed up to 24 h after the resistance exercise. However, a substantial 13+/-5% improvement in whole-body insulin sensitivity was observed, 24 h after the resistance exercise (P ¡ 0.05). This study shows that even a single session of resistance exercise improves whole-body insulin sensitivity for up to 24 h in healthy men, which is consistent with earlier observations following endurance exercise tasks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15562251,

title = {Combined Ingestion of Protein and Free Leucine with Carbohydrate Increases Postexercise Muscle Protein Synthesis in Vivo in Male Subjects},

author = {René Koopman and Anton J M Wagenmakers and Ralph J F Manders and Antoine H G Zorenc and Joan M G Senden and Marchel Gorselink and Hans A Keizer and Luc J C Loon},

doi = {10.1152/ajpendo.00413.2004},

issn = {0193-1849},

year  = {2005},

date = {2005-04-01},

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

volume = {288},

number = {4},

pages = {E645–E653},

abstract = {The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P ¡ 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P ¡ 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P ¡ 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P ¡ 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15757860,

title = {The Effects of Exercise and Adipose Tissue Lipolysis on Plasma Adiponectin Concentration and Adiponectin Receptor Expression in Human Skeletal Muscle},

author = {Chamindie Punyadeera and Antoine H G Zorenc and René Koopman and Andrew J McAinch and Egbert Smit and Ralph Manders and Hans A Keizer and David Cameron-Smith and Luc J C Loon},

doi = {10.1530/eje.1.01872},

issn = {0804-4643},

year  = {2005},

date = {2005-03-01},

journal = {European journal of endocrinology},

volume = {152},

number = {3},

pages = {427–436},

abstract = {OBJECTIVE: It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial; LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue.nnMETHODS: Ten subjects performed two exercise trials (120 min at 50% VO(2max)). Indirect calorimetry was used to determine total fat oxidation rate. Plasma samples were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin.nnRESULTS: Basal plasma adiponectin concentrations averaged 6.57+/-0.7 and 6.63+/-0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of individual muscle fibres and within the interfibrillar arterioles.nnCONCLUSION: Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of individual muscle fibres.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15165999,

title = {Combined Ingestion of Protein and Carbohydrate Improves Protein Balance during Ultra-Endurance Exercise},

author = {René Koopman and Daphne L E Pannemans and Asker E Jeukendrup and Annemie P Gijsen and Joan M G Senden and David Halliday and Wim H M Saris and Luc J C Loon and Anton J M Wagenmakers},

doi = {10.1152/ajpendo.00543.2003},

issn = {0193-1849},

year  = {2004},

date = {2004-10-01},

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

volume = {287},

number = {4},

pages = {E712–E720},

abstract = {The aims of this study were to compare different tracer methods to assess whole body protein turnover during 6 h of prolonged endurance exercise when carbohydrate was ingested throughout the exercise period and to investigate whether addition of protein can improve protein balance. Eight endurance-trained athletes were studied on two different occasions at rest (4 h), during 6 h of exercise at 50% of maximal O2 uptake (in sequential order: 2.5 h of cycling, 1 h of running, and 2.5 h of cycling), and during subsequent recovery (4 h). Subjects ingested carbohydrate (CHO trial; 0.7 g CHO.kg(-1.)h(-1)) or carbohydrate/protein beverages (CHO + PRO trial; 0.7 g CHO.kg(-1).h(-1) and 0.25 g PRO.kg(-1).h(-1)) at 30-min intervals during the entire study. Whole body protein metabolism was determined by infusion of L-[1-13C]leucine, L-[2H5]phenylalanine, and [15N2]urea tracers with sampling of blood and expired breath. Leucine oxidation increased from rest to exercise [27 +/- 2.5 vs. 74 +/- 8.8 (CHO) and 85 +/- 9.5 vs. 200 +/- 16.3 mg protein.kg(-1).h(-1) (CHO + PRO), P ¡ 0.05], whereas phenylalanine oxidation and urea production did not increase with exercise. Whole body protein balance during exercise with carbohydrate ingestion was negative (-74 +/- 8.8, -17 +/- 1.1, and -72 +/- 5.7 mg protein.kg(-1).h(-1)) when L-[1-13C]leucine, L-[2H5]phenylalanine, and [15N2]urea, respectively, were used as tracers. Addition of protein to the carbohydrate drinks resulted in a positive or less-negative protein balance (-32 +/- 16.3, 165 +/- 4.6, and 151 +/- 13.4 mg protein.kg(-1).h(-1)) when L-[1-13C]leucine, L-[2H5]phenylalanine, and [15N2]urea, respectively, were used as tracers. We conclude that, even during 6 h of exhaustive exercise in trained athletes using carbohydrate supplements, net protein oxidation does not increase compared with the resting state and/or postexercise recovery. Combined ingestion of protein and carbohydrate improves net protein balance at rest as well as during exercise and postexercise recovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15358749,

title = {Use of Intramuscular Triacylglycerol as a Substrate Source during Exercise in Humans},

author = {Luc J C Loon},

doi = {10.1152/japplphysiol.00368.2004},

issn = {8750-7587},

year  = {2004},

date = {2004-10-01},

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

volume = {97},

number = {4},

pages = {1170–1187},

abstract = {Fat and carbohydrate are the principal substrates that fuel aerobic ATP synthesis in skeletal muscle. Most endogenous fat is stored as triacylglycerol in subcutaneous and deep visceral adipose tissue. Smaller quantities of triacylglycerol are deposited as lipid droplets inside skeletal muscle fibers. The potential role of intramyocellular triacylglycerol (IMTG) as a substrate source during exercise in humans has recently regained much of its interest because of the proposed functional relationship between IMTG accumulation and the development of skeletal muscle insulin resistance. Exercise likely represents an effective means to prevent excess IMTG accretion by stimulating its rate of oxidation. However, there is much controversy on the actual contribution of the IMTG pool as a substrate source during exercise. The apparent discrepancy in the literature likely stems from methodological difficulties that have been associated with the methods used to estimate IMTG oxidation during exercise. However, recent studies using stable isotope methodology, 1H-magnetic resonance spectroscopy, and electron and/or immunofluorescence microscopy all support the contention that the IMTG pool can function as an important substrate source during exercise. Although more research is warranted, IMTG mobilization and/or oxidation during exercise seem to be largely determined by exercise intensity, exercise duration, macronutrient composition of the diet, training status, gender, and/or age. In addition, indirect evidence suggests that the capacity to mobilize and/or oxidize IMTG is substantially impaired in an obese and/or Type 2 diabetic state. As we now become aware that skeletal muscle has an enormous capacity to oxidize IMTG stores during exercise, more research is warranted to develop combined exercise, nutritional, and/or pharmacological interventions to effectively stimulate IMTG oxidation in sedentary, obese, and/or Type 2 diabetes patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15165998,

title = {Intramyocellular Lipid Content in Type 2 Diabetes Patients Compared with Overweight Sedentary Men and Highly Trained Endurance Athletes},

author = {Luc J C Loon and René Koopman and Ralph Manders and Walter Weegen and Gerrit P Kranenburg and Hans A Keizer},

doi = {10.1152/ajpendo.00464.2003},

issn = {0193-1849},

year  = {2004},

date = {2004-09-01},

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

volume = {287},

number = {3},

pages = {E558–E565},

abstract = {Recent evidence suggests that intramyocellular lipid (IMCL) accretion is associated with obesity and the development of insulin resistance and/or type 2 diabetes. However, trained endurance athletes are markedly insulin sensitive, despite an elevated mixed muscle lipid content. In an effort to explain this metabolic paradox, we compared muscle fiber type-specific IMCL storage between populations known to have elevated IMCL deposits. Immunofluorescence microscopy was performed on muscle biopsies obtained from eight highly trained endurance athletes, eight type 2 diabetes patients, and eight overweight, sedentary men after an overnight fast. Mixed muscle lipid content was substantially greater in the endurance athletes (4.0 +/- 0.4% area lipid stained) compared with the diabetes patients and the overweight men (2.3 +/- 0.4 and 2.2 +/- 0.5%, respectively). More than 40% of the greater mixed muscle lipid content was attributed to a higher proportion type I muscle fibers (62 +/- 8 vs. 38 +/- 3 and 33 +/- 7%, respectively), which contained 2.8 +/- 0.3-fold more lipid than the type II fibers. The remaining difference was explained by a significantly greater IMCL content in the type I muscle fibers of the trained athletes. Differences in IMCL content between groups or fiber types were accounted for by differences in lipid droplet density, not lipid droplet size. IMCL distribution showed an exponential increase in lipid content from the central region toward the sarcolemma, which was similar between groups and fiber types. In conclusion, IMCL contents can be substantially greater in trained endurance athletes compared with overweight and/or type 2 diabetes patients. Because structural characteristics and intramyocellular distribution of lipid aggregates seem to be similar between groups, we conclude that elevated IMCL deposits are unlikely to be directly responsible for inducing insulin resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15294047,

title = {Intramyocellular Triacylglycerol as a Substrate Source during Exercise},

author = {Luc J C Loon},

doi = {10.1079/PNS2004347},

issn = {0029-6651},

year  = {2004},

date = {2004-05-01},

journal = {The Proceedings of the Nutrition Society},

volume = {63},

number = {2},

pages = {301–307},

abstract = {The role of intramyocellular triacylglycerol (IMTG) as a substrate source during exercise has recently regained much attention as a result of the proposed functional relationship between IMTG accumulation and the development of insulin resistance. It has been speculated that elevated NEFA delivery and/or impaired fatty acid (FA) oxidation result in intramyocellular accumulation of triacylglycerol and FA metabolites, which are likely to induce defects in the insulin signalling cascade, causing insulin resistance. The progressive accumulation of IMTG in sedentary patients and patients who are obese and/or have type 2 diabetes should therefore form a major therapeutic target, and efforts should be made to develop interventions that prevent excess IMTG accretion by stimulating their rate of oxidation. Although regular exercise is likely to represent such an effective means, there is much controversy about the actual contribution of the IMTG pool as a substrate source during exercise. The apparent discrepancy in the published literature might be explained by differences in the applied research protocol and the selected subject population, but most of all by the techniques that have been employed to estimate IMTG use during exercise. Data obtained in trained-endurance athletes indicate that athletes can substantially reduce their IMTG pool following a single exercise session. With the growing awareness that skeletal muscle has a tremendous potential to oxidise IMTG during prolonged moderate-intensity exercise, more research is warranted to develop combined exercise, nutritional and/or pharmacological interventions that can stimulate IMTG oxidation in sedentary patients and patients who are obese and/or have type 2 diabetes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15119203,

title = {[Nutrition and Health–Nutrition and Performance in Sports]},

author = {W H Saris and L J Loon},

issn = {0028-2162},

year  = {2004},

date = {2004-04-01},

journal = {Nederlands tijdschrift voor geneeskunde},

volume = {148},

number = {15},

pages = {708–712},

abstract = {Optimal nutrition is an important prerequisite for a top-level performance in sports. Of primary importance in this connection is the bioavailability of carbohydrates and fats as a source of energy so that the muscles can produce ATP. The amount of glycogen in the liver and skeletal muscles and possibly the intramuscular triglyceride levels play a pivotal role in this process. Gradually decreasing the amount of training during the last 6-7 days before an important game and simultaneously increasing the amount of dietary carbohydrates results in a higher physical performance. Studies have shown that carbohydrate-electrolyte solutions with 6-8% carbohydrate by weight and an osmolarity of 250-350 mosmol/l result in a maximal carbohydrate oxidation from the solution of about 1.0-1.1 g/min and a significantly enhanced endurance. A combination of carbohydrates and proteins or amino acids has proven to be very effective to accelerate recovery after exhausting exercise. Functional food ingredients such as caffeine and creatine result in a significantly enhanced performance. This is contrast to many other ingredients and products for which the extravagant claims have not been substantiated. Hence, in addition to a few functional sports supplements for which the value has been scientifically demonstrated, sound nutrition remains an absolute prerequisite for an optimal performance in sports.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14507259,

title = {Creatine Supplementation Increases Glycogen Storage but Not GLUT-4 Expression in Human Skeletal Muscle},

author = {Luc J C Loon and Robyn Murphy and Audrey M Oosterlaar and David Cameron-Smith and Mark Hargreaves and Anton J M Wagenmakers and Rodney Snow},

doi = {10.1042/CS20030116},

issn = {0143-5221},

year  = {2004},

date = {2004-01-01},

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

volume = {106},

number = {1},

pages = {99–106},

abstract = {It has been speculated that creatine supplementation affects muscle glucose metabolism in humans by increasing muscle glycogen storage and up-regulating GLUT-4 protein expression. In the present study, we assessed the effects of creatine loading and prolonged supplementation on muscle glycogen storage and GLUT-4 mRNA and protein content in humans. A total of 20 subjects participated in a 6-week supplementation period during which creatine or a placebo was ingested. Muscle biopsies were taken before and after 5 days of creatine loading (20 g.day(-1)) and after 6 weeks of continued supplementation (2 g.day(-1)). Fasting plasma insulin concentrations, muscle creatine, glycogen and GLUT-4 protein content as well as GLUT-4, glycogen synthase-1 (GS-1) and glycogenin-1 (Gln-1) mRNA expression were determined. Creatine loading significantly increased total creatine, free creatine and creatine phosphate content with a concomitant 18 +/- 5% increase in muscle glycogen content (P¡0.05). The subsequent use of a 2 g.day(-1) maintenance dose for 37 days did not maintain total creatine, creatine phosphate and glycogen content at the elevated levels. The initial increase in muscle glycogen accumulation could not be explained by an increase in fasting plasma insulin concentration, muscle GLUT-4 mRNA and/or protein content. In addition, neither muscle GS-1 nor Gln-1 mRNA expression was affected. We conclude that creatine ingestion itself stimulates muscle glycogen storage, but does not affect muscle GLUT-4 expression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12923116,

title = {Intramyocellular Lipid Content Is Increased after Exercise in Nonexercising Human Skeletal Muscle},

author = {V B Schrauwen-Hinderling and L J C Loon and R Koopman and K Nicolay and W H M Saris and M E Kooi},

doi = {10.1152/japplphysiol.00304.2003},

issn = {8750-7587},

year  = {2003},

date = {2003-12-01},

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

volume = {95},

number = {6},

pages = {2328–2332},

abstract = {Intramyocellular lipid (IMCL) content has been reported to decrease after prolonged submaximal exercise in active muscle and, therefore, seems to form an important local substrate source. Because exercise leads to a substantial increase in plasma free fatty acid (FFA) availability with a concomitant increase in FFA uptake by muscle tissue, we aimed to investigate potential differences in the net changes in IMCL content between contracting and noncontracting skeletal muscle after prolonged endurance exercise. IMCL content was quantified by magnetic resonance spectroscopy in eight trained cyclists before and after a 3-h cycling protocol (55% maximal energy output) in the exercising vastus lateralis and the nonexercising biceps brachii muscle. Blood samples were taken before and after exercise to determine plasma FFA, glycerol, and triglyceride concentrations, and substrate oxidation was measured with indirect calorimetry. Prolonged endurance exercise resulted in a 20.4 +/- 2.8% (P ¡ 0.001) decrease in IMCL content in the vastus lateralis muscle. In contrast, we observed a substantial (37.9 +/- 9.7%; P ¡ 0.01) increase in IMCL content in the less active biceps brachii muscle. Plasma FFA and glycerol concentrations were substantially increased after exercise (from 85 +/- 6 to 1450 +/- 55 and 57 +/- 11 to 474 +/- 54 microM, respectively; P ¡ 0.001), whereas plasma triglyceride concentrations were decreased (from 1498 +/- 39 to 703 +/- 7 microM; P ¡ 0.001). IMCL is an important substrate source during prolonged moderate-intensity exercise and is substantially decreased in the active vastus lateralis muscle. However, prolonged endurance exercise with its concomitant increase in plasma FFA concentration results in a net increase in IMCL content in less active muscle.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14514877,

title = {Intramyocellular Lipids Form an Important Substrate Source during Moderate Intensity Exercise in Endurance-Trained Males in a Fasted State},

author = {Luc J C Loon and Rene Koopman and Jos H C H Stegen and Anton J M Wagenmakers and Hans A Keizer and Wim H M Saris},

doi = {10.1113/jphysiol.2003.052431},

issn = {0022-3751},

year  = {2003},

date = {2003-12-01},

journal = {The Journal of physiology},

volume = {553},

number = {Pt 2},

pages = {611–625},

abstract = {Both stable isotope methodology and fluorescence microscopy were applied to define the use of intramuscular triglyceride (IMTG) stores as a substrate source during exercise on a whole-body as well as on a fibre type-specific intramyocellular level in trained male cyclists. Following an overnight fast, eight subjects were studied at rest, during 120 min of moderate intensity exercise (60 % maximal oxygen uptake capacity (VO2,max)) and 120 min of post-exercise recovery. Continuous infusions of [U-13C]palmitate and [6,6-2H2]glucose were administered at rest and during subsequent exercise to quantify whole-body plasma free fatty acid (FFA) and glucose oxidation rates and the contribution of other fat sources (sum of muscle- plus lipoprotein-derived TG) and muscle glycogen to total energy expenditure. Fibre type-specific intramyocellular lipid content was determined in muscle biopsy samples collected before, immediately after and 2 h after exercise. At rest, fat oxidation provided 66 +/- 5 % of total energy expenditure, with FFA and other fat sources contributing 48 +/- 6 and 17 +/- 3 %, respectively. FFA oxidation rates increased during exercise, and correlated well with the change in plasma FFA concentrations. Both the use of other fat sources and muscle glycogen declined with the duration of exercise, whereas plasma glucose production and utilisation increased (P ¡ 0.001). On average, FFA, other fat sources, plasma glucose and muscle glycogen contributed 28 +/- 3, 15 +/- 2, 12 +/- 1 and 45 +/- 4 % to total energy expenditure during exercise, respectively. Fluorescence microscopy revealed a 62 +/- 7 % net decline in muscle lipid content following exercise in the type I fibres only, with no subsequent change during recovery. We conclude that IMTG stores form an important substrate source during moderate intensity exercise in endurance-trained male athletes following an overnight fast, with the oxidation rate of muscle- plus lipoprotein-derived TG being decreased with the duration of exercise.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vanloon2003,

title = {Influence of Prolonged Endurance Cycling and Recovery Diet on Intramuscular Triglyceride Content in Trained Males},

author = {Luc J. C. Loon and Vera B. Schrauwen-Hinderling and René Koopman and Anton J. M. Wagenmakers and Matthijs K. C. Hesselink and Gert Schaart and M. Eline Kooi and Wim H. M. Saris},

doi = {10.1152/ajpendo.00112.2003},

year  = {2003},

date = {2003-10-01},

journal = {American Journal of Physiology-endocrinology and Metabolism},

volume = {285},

number = {4},

abstract = {Intramuscular triglycerides (IMTG) are assumed to form an important substrate source during prolonged endurance exercise in trained males. This study investigated the effects of endurance exercise ...},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12682837,

title = {The Use of the [1,2-13C]Acetate Recovery Factor in Metabolic Research},

author = {Luc J C Loon and Rene Koopman and Patrick Schrauwen and Jos Stegen and Anton J M Wagenmakers},

doi = {10.1007/s00421-003-0810-x},

issn = {1439-6319},

year  = {2003},

date = {2003-05-01},

journal = {European journal of applied physiology},

volume = {89},

number = {3-4},

pages = {377–383},

abstract = {To provide guidelines on the correct application of the acetate recovery factor in metabolic research, we investigated the influence of exercise intensity and infusion protocol on [1,2-(13)C]acetate label recovery during exercise. Eight cyclists were studied during [1,2-(13)C]acetate infusion for 1 h at rest followed by three 30-min stages of cycling exercise at a workload of 40, 55 and 75% maximal workload ( W(max)), respectively (protocol 1). Four cyclists were subsequently studied following [1,2-(13)C]acetate infusion in three separate trials while cycling at the same workloads but in the absence of any pre-exercise infusion period (protocol 2). Finally, we observed the cyclists during [1,2-(13)C]acetate infusion at a 40% W(max) workload after 4 h of pre-exercise infusion (protocol 3). Acetate recovery increased from 13.7 (0.4)%, after 1 h of rest, to a plateau value of 75.1 (2), 91.2 (0.7) and 101 (2)% during exercise at 40, 55 and 75% W(max) workloads, respectively. In protocol 2, without prior infusion time, fractional label recovery was substantially lower at each separate workload. In contrast, when applying an extensive pre-exercise infusion period of 4 h, acetate recovery rates were substantially increased compared to the values observed in protocols 1 and 2 during exercise at a 40% W(max) workload. In conclusion, in contrast to resting conditions, acetate recovery reaches a plateau value during exercise. Though this plateau value is repeatedly used to correct for label recovery in various exercise studies, our data clearly show that acetate label recovery during exercise not only depends on the exercise intensity but also on the applied infusion protocol. Therefore, theoretical acetate recovery factors taken from previous literature are not generally applicable.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12610012,

title = {Amino Acid Ingestion Strongly Enhances Insulin Secretion in Patients with Long-Term Type 2 Diabetes},

author = {Luc J C Loon and Margriet Kruijshoop and Paul P C A Menheere and Anton J M Wagenmakers and Wim H M Saris and Hans A Keizer},

doi = {10.2337/diacare.26.3.625},

issn = {0149-5992},

year  = {2003},

date = {2003-03-01},

journal = {Diabetes Care},

volume = {26},

number = {3},

pages = {625–630},

abstract = {OBJECTIVE: Insulin secretion in response to carbohydrate intake is blunted in type 2 diabetic patients. However, it is not clear whether the insulin response to other stimuli, such as amino acids, is also diminished. Recently, we defined an optimal insulinoptropic mixture containing free leucine, phenylalanine, and a protein hydrolysate that substantially enhances the insulin response in healthy young subjects when coingested with carbohydrate. In this study, we aimed to investigate the insulinotropic capacity of this mixture in long-term type 2 diabetic patients.nnRESEARCH DESIGN AND METHODS: Ten type 2 diabetic patients (aged 59.1 +/- 2.0 years, BMI 26.5 +/- 0.7 kg/m(2)) and 10 healthy control subjects (58.8 +/- 2.1 years, 26.5 +/- 0.7 kg/m(2)) visited our lab twice, during which insulin responses were determined following ingestion of carbohydrate only (CHO) or carbohydrate with the free amino acid/protein mixture (CHO+PRO). All subjects received 0.7 g x kg(-1) x h(-1) carbohydrate with or without 0.35 g x kg(-1) x h(-1) of the amino acid/protein mixture.nnRESULTS: Insulin responses were dramatically increased in the CHO+PRO trial in both the type 2 diabetic and control groups (189 and 114%, respectively) compared with the CHO trial (P ¡ 0.01). Plasma glucose, glucagon, growth hormone, cortisol, IGF-I, and IGF binding protein 3 responses were not different between trials within the 2-h time frame.nnCONCLUSIONS: The insulin secretory capacity in long-term type 2 diabetic patients is substantially underestimated, as the insulin response following carbohydrate intake can be nearly tripled by coingestion of a free amino acid/protein mixture. Future research should be performed to investigate whether such nutritional interventions can improve postprandial glucose disposal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12546637,

title = {Effects of Creatine Loading and Prolonged Creatine Supplementation on Body Composition, Fuel Selection, Sprint and Endurance Performance in Humans},

author = {Luc J C Loon and Audrey M Oosterlaar and Fred Hartgens and Matthijs K C Hesselink and Rodney J Snow and Anton J M Wagenmakers},

doi = {10.1042/CS20020159},

issn = {0143-5221},

year  = {2003},

date = {2003-02-01},

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

volume = {104},

number = {2},

pages = {153–162},

abstract = {Most research on creatine has focused on short-term creatine loading and its effect on high-intensity performance capacity. Some studies have investigated the effect of prolonged creatine use during strength training. However, studies on the effects of prolonged creatine supplementation are lacking. In the present study, we have assessed the effects of both creatine loading and prolonged supplementation on muscle creatine content, body composition, muscle and whole-body oxidative capacity, substrate utilization during submaximal exercise, and on repeated supramaximal sprint, as well as endurance-type time-trial performance on a cycle ergometer. Twenty subjects ingested creatine or a placebo during a 5-day loading period (20 g.day(-1)) after which supplementation was continued for up to 6 weeks (2 g.day(-1)). Creatine loading increased muscle free creatine, creatine phosphate (CrP) and total creatine content ( P ¡0.05). The subsequent use of a 2 g.day(-1) maintenance dose, as suggested by an American College of Sports Medicine Roundtable, resulted in a decline in both the elevated CrP and total creatine content and maintenance of the free creatine concentration. Both short- and long-term creatine supplementation improved performance during repeated supramaximal sprints on a cycle ergometer. However, whole-body and muscle oxidative capacity, substrate utilization and time-trial performance were not affected. The increase in body mass following creatine loading was maintained after 6 weeks of continued supplementation and accounted for by a corresponding increase in fat-free mass. This study provides definite evidence that prolonged creatine supplementation in humans does not increase muscle or whole-body oxidative capacity and, as such, does not influence substrate utilization or performance during endurance cycling exercise. In addition, our findings suggest that prolonged creatine ingestion induces an increase in fat-free mass.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11579177,

title = {The Effects of Increasing Exercise Intensity on Muscle Fuel Utilisation in Humans},

author = {L J Loon and P L Greenhaff and D Constantin-Teodosiu and W H Saris and A J Wagenmakers},

doi = {10.1111/j.1469-7793.2001.00295.x},

issn = {0022-3751},

year  = {2001},

date = {2001-10-01},

journal = {The Journal of physiology},

volume = {536},

number = {Pt 1},

pages = {295–304},

abstract = {1. Contemporary stable isotope methodology was applied in combination with muscle biopsy sampling to accurately quantify substrate utilisation and study the regulation of muscle fuel selection during exercise. 2. Eight cyclists were studied at rest and during three consecutive 30 min stages of exercise at intensities of 40, 55 and 75 % maximal workload (W(max)). A continuous infusion of [U-(13)C]palmitate and [6,6-(2)H(2)]glucose was administered to determine plasma free fatty acid (FFA) oxidation and estimate plasma glucose oxidation, respectively. Biopsy samples were collected before and after each exercise stage. 3. Muscle glycogen and plasma glucose oxidation rates increased with every increment in exercise intensity. Whole-body fat oxidation increased to 32 +/- 2 kJ min(-1) at 55 % W(max), but declined at 75 % W(max) (19 +/- 2 kJ min(-1)). This decline involved a decrease in the oxidation rate of both plasma FFA and triacylglycerol fat sources (sum of intramuscular plus lipoprotein-derived triacylglycerol), and was accompanied by increases in muscle pyruvate dehydrogenase complex activation and acetylation of the carnitine pool, resulting in a decline in muscle free carnitine concentration. 4. We conclude that the most likely mechanism for the reduction in fat oxidation during high-intensity exercise is a downregulation of carnitine palmitoyltransferase I, either by this marked decline in free carnitine availability or by a decrease in intracellular pH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{jentjens2001,

title = {Addition of Protein and Amino Acids to Carbohydrates Does Not Enhance Postexercise Muscle Glycogen Synthesis.},

author = {Roy L. P. G. Jentjens and Luc J. C. Loon and Christopher H. Mann and Anton J. M. Wagenmakers and Asker E. Jeukendrup},

doi = {10.1152/jappl.2001.91.2.839},

year  = {2001},

date = {2001-08-01},

journal = {Journal of Applied Physiology},

volume = {91},

number = {2},

pages = {839–846},

abstract = {Ingestion of a protein-amino acid mixture (Pro; wheat protein hydrolysate, leucine, and phenylalanine) in combination with carbohydrate (CHO; 0.8 g $cdot$ kg-1 $cdot$ h-1) has been shown to increase muscle g...},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11101469,

title = {Effects of Acute (-)-Hydroxycitrate Supplementation on Substrate Metabolism at Rest and during Exercise in Humans},

author = {L J Loon and J J Rooijen and B Niesen and H Verhagen and W H Saris and A J Wagenmakers},

doi = {10.1093/ajcn/72.6.1445},

issn = {0002-9165},

year  = {2000},

date = {2000-12-01},

journal = {The American journal of clinical nutrition},

volume = {72},

number = {6},

pages = {1445–1450},

abstract = {BACKGROUND: (-)-Hydroxycitrate (HCA), a competitive inhibitor of ATP-citrate lyase, should reduce the extramitochondrial acetyl-CoA pool. It has been hypothesized that HCA ingestion can reduce malonyl-CoA concentrations and consequently increase fatty acid oxidation in vivo.nnOBJECTIVE: This study investigated the acute effects of HCA supplementation on substrate utilization at rest and during exercise in endurance-trained humans.nnDESIGN: Ten cyclists [x+/- SD) age: 24 +/- 2 y, weight: 73 +/- 2 kg, maximal oxygen uptake: 4.95 +/- 0.11 L/min, maximal work output (W:max): 408 +/- 8 W] were studied at rest and during 2 h of exercise at 50% W:max on 2 occasions. Both 45 and 15 min before exercise and 30 and 60 min after the start of exercise, 3.1 mL/kg body wt of an HCA solution (19 g/L) or placebo was ingested. Total fat and carbohydrate oxidation rates were assessed. Blood samples were collected at 15-min intervals at rest and every 30 min during exercise.nnRESULTS: Plasma HCA concentrations increased after HCA ingestion up to 0.39 +/- 0.02 mmol/L (82.0 +/- 4.8 mg/L). However, no significant differences in total fat and carbohydrate oxidation rates were observed between trials. Accordingly, plasma glucose, glycerol, and fatty acid concentrations did not differ between trials. Plasma lactate concentrations were significantly lower in the HCA than in the placebo trial after 30 min of exercise but at the end of the exercise period they did not differ between trials.nnCONCLUSION: HCA, even when provided in large quantities, does not increase total fat oxidation in vivo in endurance-trained humans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11015482,

title = {Ingestion of Protein Hydrolysate and Amino Acid-Carbohydrate Mixtures Increases Postexercise Plasma Insulin Responses in Men},

author = {L J Loon and M Kruijshoop and H Verhagen and W H Saris and A J Wagenmakers},

doi = {10.1093/jn/130.10.2508},

issn = {0022-3166},

year  = {2000},

date = {2000-10-01},

journal = {The Journal of nutrition},

volume = {130},

number = {10},

pages = {2508–2513},

abstract = {To optimize the postexercise insulin response and to increase plasma amino acid availability, we studied postexercise insulin levels after the ingestion of carbohydrate and wheat protein hydrolysate with and without free leucine and phenylalanine. After an overnight fast, eight male cyclists visited our laboratory on five occasions, during which a control drink and two different beverage compositions in two different doses were tested. After they performed a glycogen-depletion protocol, subjects received a beverage (3.5 mL. kg(-1)) every 30 min to ensure an intake of 1.2 g. kg(-1). h(-1) carbohydrate and 0, 0.2 or 0.4 g. kg(-1). h(-1) protein hydrolysate (and amino acid) mixture. After the insulin response was expressed as the area under the curve, only the ingestion of the beverages containing wheat protein hydrolysate, leucine and phenylalanine resulted in a marked increase in insulin response (+52 and + 107% for the 0.2 and 0.4 g. kg(-1). h(-1) mixtures, respectively; P: ¡ 0. 05) compared with the carbohydrate-only trial). A dose-related effect existed because doubling the dose (0.2-0.4 g. kg(-1). h(-1)) led to an additional rise in insulin response (P: ¡ 0.05). Plasma leucine, phenylalanine and tyrosine concentrations showed strong correlations with the insulin response (P: ¡ 0.0001). This study provides a practical tool to markedly elevate insulin levels and plasma amino acid availability through dietary manipulation, which may be of great value in clinical nutrition, (recovery) sports drinks and metabolic research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vanloon2000,

title = {Maximizing Postexercise Muscle Glycogen Synthesis: Carbohydrate Supplementation and the Application of Amino Acid or Protein Hydrolysate Mixtures},

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

doi = {10.1093/ajcn/72.1.106},

year  = {2000},

date = {2000-07-01},

journal = {The American Journal of Clinical Nutrition},

volume = {72},

number = {1},

pages = {106–111},

abstract = {Background: Postexercise muscle glycogen synthesis is an important factor in determining the time needed to recover from prolonged exercise. Objective: This study investigated whether an increase in carbohydrate intake, ingestion of a mixture of protein hydrolysate and amino acids in combination with carbohydrate, or both results in higher postexercise muscle glycogen synthesis rates than does ingestion of 0.8 g.kg -1 .h -1 carbohydrate, provided at 30-min intervals. Design: Eight trained cyclists visited the laboratory 3 times, during which a control beverage and 2 other beverages were tested. After the subjects participated in a strict glycogen-depletion protocol, muscle biopsy samples were collected. The subjects received a beverage every 30 min to ensure ingestion of 0.8 g carbohydrate.kg -1 .h -1 (Carb trial), 0,8 g carbohydrate.kg -1 .h -1 plus 0.4 g wheat protein hydrolysate plus free leucine and phenylalanine . kg -1 . h -1 (proven to be highly insulinotropic; Carb + Pro trial), or 1.2 g carbohydrate . kg -1 . h -1 (Carb + Carb trial). After 5 h, a second biopsy was taken. Results: Plasma insulin responses in the Carb + Pro and Carb + Carb trials were higher than those in the Carb trial (88 ± 17% and 46 ± 18%: P $<$ 0.05). Muscle glycogen synthesis was higher in both trials than in the Carb trial (35. 4 ± 5.1 and 44.8 ± 6.8 compared with 16.6 ± 7.8 μmol glycosol units. g dry wt -1 . h -1 , respectively; P $<$ 0.05). Conclusions: Addition of a mixture of protein hydrolysate and amino acids to a carbohydrate-containing solution (at an intake of 0.8 g carbohydrate. kg -1 .h -1 can stimulate glycogen synthesis. However, glycogen synthesis can also be accelerated by increasing carbohydrate intake (0.4 g. kg -1 . h -1 ) when supplements are provided at 30-min intervals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid10871567,

title = {Plasma Insulin Responses after Ingestion of Different Amino Acid or Protein Mixtures with Carbohydrate},

author = {L J Loon and W H Saris and H Verhagen and A J Wagenmakers},

doi = {10.1093/ajcn/72.1.96},

issn = {0002-9165},

year  = {2000},

date = {2000-07-01},

journal = {The American journal of clinical nutrition},

volume = {72},

number = {1},

pages = {96–105},

abstract = {BACKGROUND: Protein induces an increase in insulin concentrations when ingested in combination with carbohydrate. Increases in plasma insulin concentrations have been observed after the infusion of free amino acids. However, the insulinotropic properties of different amino acids or protein (hydrolysates) when co-ingested with carbohydrate have not been investigated.nnOBJECTIVE: The aim of this study was to define an amino acid and protein (hydrolysate) mixture with a maximal insulinotropic effect when co-ingested with carbohydrate.nnDESIGN: Eight healthy, nonobese male subjects visited our laboratory, after an overnight fast, on 10 occasions on which different beverage compositions were tested for 2 h. During those trials the subjects ingested 0.8 g*kg(-)(1)*h(-)(1) carbohydrate and 0.4 g*kg(-)(1)*h(-)(1) of an amino acid and protein (hydrolysate) mixture.nnRESULTS: A strong initial increase in plasma glucose and insulin concentrations was observed in all trials, after which large differences in insulin response between drinks became apparent. After we expressed the insulin response as area under the curve during the second hour, ingestion of the drinks containing free leucine, phenylalanine, and arginine and the drinks with free leucine, phenylalanine, and wheat protein hydrolysate were followed by the largest insulin response (101% and 103% greater, respectively, than with the carbohydrate-only drink; P ¡ 0.05).nnCONCLUSIONS: Insulin responses are positively correlated with plasma leucine, phenylalanine, and tyrosine concentrations. A mixture of wheat protein hydrolysate, free leucine, phenylalanine, and carbohydrate can be applied as a nutritional supplement to strongly elevate insulin concentrations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid10517772,

title = {Effect of Training Status on Fuel Selection during Submaximal Exercise with Glucose Ingestion},

author = {L J Loon and A E Jeukendrup and W H Saris and A J Wagenmakers},

doi = {10.1152/jappl.1999.87.4.1413},

issn = {8750-7587},

year  = {1999},

date = {1999-10-01},

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

volume = {87},

number = {4},

pages = {1413–1420},

abstract = {In this study, an oral glucose load was enriched with a [U-(13)C]glucose tracer to determine differences in substrate utilization between endurance-trained (T) and untrained (UT) subjects during submaximal exercise at the same relative and absolute workload when glucose is ingested. Six highly trained cyclists/triathletes [maximal workload (Wmax), 400 +/- 9 W] and seven UT subjects (Wmax, 296 +/- 8 W) were studied during 120 min of cycling exercise at 50% Wmax ( approximately 55% maximal O(2) consumption). The T subjects performed a second trial at the mean workload of the UT group (148 +/- 4 W). Before exercise, 8.0 ml/kg of a (13)C-enriched glucose solution (80 g/l) was ingested. During exercise, boluses of 2.0 ml/kg of the same solution were administered every 15 min. Measurements were made in the 90- to 120-min period when a steady state was present in breath (13)CO(2) and plasma glucose (13)C enrichment. Energy expenditure was higher in T than in UT subjects (58 vs. 47 kJ/min, respectively; P ¡ 0.001) at the same relative intensity. This was completely accounted for by an increased fat oxidation (0.57 vs. 0.40 g/min; P ¡ 0.01). At the same absolute intensity, fat oxidation contributed more to energy expenditure in the T compared with the UT group (44 vs. 33%, respectively; P ¡ 0.01). The reduction in carbohydrate oxidation in the T group was explained by a diminished oxidation rate of muscle glycogen (indirectly assessed by using tracer methodology at 0.72 +/- 0.1 and 1.03 +/- 0.1 g/min, respectively; P ¡ 0.01) and liver-derived glucose (0.15 +/- 0.03 and 0.22 +/- 0.02 g/min, respectively; P ¡ 0.05). Exogenous glucose oxidation rates were similar during all trials (+/-0.70 g/min).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}