Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity.

UNLABELLED We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). IN CONCLUSION (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.

[1]  R. DeFronzo,et al.  Increased insulin sensitivity and insulin binding to monocytes after physical training. , 1979, The New England journal of medicine.

[2]  W. M. Sherman,et al.  Exercise training increases glucose transporter protein GLUT‐4 in skeletal muscle of obese Zucker (fa/fa) rats , 1990, FEBS letters.

[3]  R. H. Rochelle,et al.  Exercise blood flow changes in the human forearm during physical t raining. , 1963, Journal of applied physiology.

[4]  B. Desbuquois,et al.  Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. , 1971, The Journal of clinical endocrinology and metabolism.

[5]  G. Dalsky,et al.  Insulin action and secretion in endurance-trained and untrained humans. , 1987, Journal of applied physiology.

[6]  H. Yki-Jărvinen,et al.  Mechanisms of Hyperglycemia-Induced Insulin Resistance in Whole Body and Skeletal Muscle of Type I Diabetic Patients , 1992, Diabetes.

[7]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[8]  L. Korányi,et al.  Exercise reduces muscle glucose transport protein (GLUT-4) mRNA in type 1 diabetic patients. , 1993, Journal of applied physiology.

[9]  R. DeFronzo,et al.  Physical training and insulin sensitivity. , 1986, Diabetes/metabolism reviews.

[10]  D. James,et al.  Effects of Exercise Training on Insulin-Regulatable Glucose-Transporter Protein Levels in Rat Skeletal Muscle , 1990, Diabetes.

[11]  L. Groop,et al.  Impaired Activation of Glycogen Synthase in People at Increased Risk for Developing NIDDM , 1992, Diabetes.

[12]  E. Sugimoto,et al.  Decrease in muscle glucose transporter number in chronic physical inactivity in rats. , 1991, The American journal of physiology.

[13]  E. Horton,et al.  Exercise training increases the number of glucose transporters in rat adipose cells. , 1989, The American journal of physiology.

[14]  C. G. Blomqvist,et al.  Maximal vascular leg conductance in trained and untrained men. , 1987, Journal of applied physiology.

[15]  J. Henriksson,et al.  Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise , 1977, The Journal of physiology.

[16]  B. Saltin,et al.  Skeletal Muscle Adaptability: Significance for Metabolism and Performance , 1985 .

[17]  M. Laakso,et al.  Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. , 1990, The Journal of clinical investigation.

[18]  H. Lodish,et al.  Molecular Physiology of Glucose Transporters , 1990, Diabetes Care.

[19]  P. Schantz,et al.  Adaptation of human skeletal muscle to endurance training of long duration. , 1983, Clinical physiology.

[20]  H. Wallberg-henriksson,et al.  Glucose transport into rat skeletal muscle: interaction between exercise and insulin. , 1988, Journal of applied physiology.

[21]  P. Andersen,et al.  Capillary density in skeletal muscle of man. , 1975, Acta physiologica Scandinavica.

[22]  D. R. Coles,et al.  The source of blood samples withdrawn from deep forearm veins via catheters passed upstream from the median cubital vein , 1958, The Journal of physiology.

[23]  M. Laakso,et al.  Kinetics of In Vivo Muscle Insulin-Mediated Glucose Uptake in Human Obesity , 1990, Diabetes.

[24]  J A Hodgdon,et al.  Lean body mass estimation by bioelectrical impedance analysis: a four-site cross-validation study. , 1988, The American journal of clinical nutrition.

[25]  H. Galbo,et al.  Effect of physical exercise on sensitivity and responsiveness to insulin in humans. , 1988, The American journal of physiology.

[26]  E. Ferrannini The theoretical bases of indirect calorimetry: a review. , 1988, Metabolism: clinical and experimental.

[27]  M. Laakso,et al.  Kinetics of Insulin-Mediated and Non-Insulin-Mediated Glucose Uptake in Humans , 1990, Diabetes.

[28]  E. Hultman,et al.  Muscle Glycogen Synthesis after Exercise : an Enhancing Factor localized to the Muscle Cells in Man , 1966, Nature.

[29]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[30]  P. Neufer,et al.  Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men. , 1991, The American journal of physiology.

[31]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[32]  T. Ohkuwa,et al.  Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle. , 1990, The American journal of physiology.

[33]  H. Yki-Järvinen,et al.  Effects of Body Composition on Insulin Sensitivity , 1983, Diabetes.

[34]  P. Andersen,et al.  Training induced changes in the subgroups of human type II skeletal muscle fibres. , 1977, Acta physiologica Scandinavica.

[35]  E. Newsholme,et al.  The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. , 1963, Lancet.

[36]  E. Horton,et al.  Glucose transporter number, activity, and isoform content in plasma membranes of red and white skeletal muscle. , 1991, The American journal of physiology.

[37]  F. Liebold,et al.  Diminished insulin response in highly trained athletes. , 1978, Metabolism: clinical and experimental.

[38]  H. Wallberg-henriksson,et al.  Reversal of the exercise-induced increase in muscle permeability to glucose. , 1987, The American journal of physiology.

[39]  E. Horton,et al.  Glucose Transporter Number, Function, and Subcellular Distribution in Rat Skeletal Muscle After Exercise Training , 1992, Diabetes.

[40]  R. DeFronzo,et al.  The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization , 1981, Diabetes.

[41]  M. Houston,et al.  Cross-adaptive responses to different forms of leg training: skeletal muscle biochemistry and histochemistry. , 1982, Canadian journal of physiology and pharmacology.

[42]  P. Björntorp,et al.  Tissue uptake of insulin and inulin in red and white skeletal muscle in vivo. , 1992, The American journal of physiology.