Physical Activity and Exercise

Exercise and Insulin Resistance

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Muscle is the main site of insulin-stimulated glucose disposal (44), and the transport of glucose across the plasma membrane appears to be key for glucose disposal in healthy (45) and diabetic (46) subjects. Glucose diffuses into the muscle through glucose transporter proteins (of which GLUT4 is the main isoform), which are translocated to the muscle membrane upon stimulation by insulin (47). It has been shown that insulin stimulation in diabetic subjects fails to induce normal GLUT4 protein translocation to the muscle membrane (48), thereby limiting glucose diffusion into the muscle. Given this, one potential mechanism underlying enhanced glucose disposal after an acute bout of exercise may be increased translocation of GLUT4 into the sarcolemma and T-tubules of the muscle. Indeed, a single one-hour session of moderate-intensity cycling has been shown to increase the amount of GLUT4 protein in the muscle membrane by almost 75% in a sample of type 2 diabetics and similarly in healthy subjects (49). Exactly why GLUT4 translocation to the muscle membrane is enhanced post exercise is unclear, but the effect may be due to muscle contraction (50), hypoxia (51), or others (52). 

Reference

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44. Baron AD, Brechtel G, Wallace P, et al. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol 1988; 255: E769-74.

45. Fink RI, Wallace P, Brechtel G, et al. Evidence that glucose transport is rate-limiting for in vivo glucose uptake. Metabolism 1992; 41: 897-902.

46. Butler PC, Kryshak EJ, Marsh M, et al. Effect of insulin on oxidation of intracellularly and extracellularly derived glucose in patients with NIDDM. Evidence for primary defect in glucose transport and/or phosphorylation but not oxidation. Diabetes 1990; 39: 1373-80.

47. Shepherd PR and Kahn BB. Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus. N Engl J Med 1999; 341: 248-57.

48. Ryder JW, Yang J, Galuska D, et al. Use of a novel impermeable biotinylated photolabeling reagent to assess insulin- and hypoxia-stimulated cell surface GLUT4 content in skeletal muscle from type 2 diabetic patients. Diabetes 2000; 49: 647-54.

49. Kennedy JW, Hirshman MF, Gervino EV, et al. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes 1999; 48: 1192-7.

50. Gao J, Ren J, Gulve EA, et al. Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma. J Appl Physiol 1994; 77: 1597-601.

51. Cartee GD, Douen AG, Ramlal T, et al. Stimulation of glucose transport in skeletal muscle by hypoxia. J Appl Physiol 1991; 70: 1593-600.

52. Etgen GJ, Jr., Fryburg DA and Gibbs EM. Nitric oxide stimulates skeletal muscle glucose transport through a calcium/contraction- and phosphatidylinositol-3-kinase-independent pathway. Diabetes 1997; 46: 1915-9.

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