Journal of Clinical Endocrinology & Metabolism, Vol 80, 2437-2446, Copyright © 1995 by Endocrine Society

ARTICLES

Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT 4 in skeletal muscles

DS Hardin, B Azzarelli, J Edwards, J Wigglesworth, L Maianu, G Brechtel, A Johnson, A Baron and WT Garvey
Department of Pediatrics, University of Texas Medical School, Houston 77030, USA.

Exercise is associated with increased insulin sensitivity. To better understand mechanisms that could be responsible for this association, we studied seven controls and seven endurance-trained athletes. A 600 mU/m2.min hyperinsulinemic euglycemic glucose clamp with the limb balance technique assessed insulin sensitivity as whole body glucose uptake (WBGU) and leg glucose uptake (LGU). Indirect calorimetry and hemodynamic measurements, such as leg blood flow (LBF) and cardiac output, were performed at baseline and maximal insulin stimulation. The content of the glucose transporter GLUT 4 and muscle fiber type were evaluated in three muscle groups: vastus lateralis, gastrocnemius, and biceps. Athletes exhibited 35% higher WBGU and 30% higher LGU than controls. Basal LBF (liters per min) was higher in athletes, but the difference was not statistically significant. After insulin stimulation, LBF was 31% higher in athletes than controls (P = 0.05). Indirect calorimetry revealed that athletes had a 44% higher rate of nonoxidative glucose metabolism than controls (P = 0.01). GLUT 4 levels in vastus were 90% (P < 0.05) greater in athletes, whereas smaller differences were noted between athletes and controls in biceps and gastrocnemius. Importantly, the vastus lateralis GLUT 4 content was correlated with WBGU (r = 0.60; P < 0.05) and LGU (r = 0.62; P < 0.05). Relative numbers of oxidative fibers were increased in vastus from athletes and were positively correlated with maximal oxygen consumption (VO2 max), but GLUT 4 content could not be correlated with oxidative fiber content in individual controls or athletes. We conclude that in humans 1) endurance training enhances insulin's ability to increase LBF; 2) GLUT 4 is differentially expressed as a function of muscle group and is up-regulated by exercise in a muscle-specific manner; 3) in vastus lateralis, GLUT 4 levels are well correlated with insulin- stimulated rates of both WBGU and LGU; and 4) GLUT 4 content and in vivo insulin sensitivity do not vary as a function of fiber type composition. Thus, blood flow and GLUT 4 expression in muscle are important mechanisms that mediate greater insulin sensitivity in athletes.

This article has been cited by other articles:

				R. Muniyappa, M. Montagnani, K. K. Koh, and M. J. Quon Cardiovascular Actions of Insulin Endocr. Rev., August 1, 2007; 28(5): 463 - 491. [Abstract] [Full Text] [PDF]

				C. Frosig, A. J. Rose, J. T. Treebak, B. Kiens, E. A. Richter, and J. F.P. Wojtaszewski Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle: Interactions at the Level of Phosphatidylinositol 3-Kinase, Akt, and AS160 Diabetes, August 1, 2007; 56(8): 2093 - 2102. [Abstract] [Full Text] [PDF]

				F. Ohta, T. Takagi, H. Sato, and L. J. Ignarro Low-dose L-arginine administration increases microperfusion of hindlimb muscle without affecting blood pressure in rats PNAS, January 23, 2007; 104(4): 1407 - 1411. [Abstract] [Full Text] [PDF]

				M. G. Clark, M. G. Wallis, E. J. Barrett, M. A. Vincent, S. M. Richards, L. H. Clerk, and S. Rattigan Blood flow and muscle metabolism: a focus on insulin action Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E241 - E258. [Abstract] [Full Text] [PDF]

				D. J. Angus, M. A. Febbraio, and M. Hargreaves Plasma glucose kinetics during prolonged exercise in trained humans when fed carbohydrate Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E573 - E577. [Abstract] [Full Text] [PDF]

				B. H. Goodpaster, J. He, S. Watkins, and D. E. Kelley Skeletal Muscle Lipid Content and Insulin Resistance: Evidence for a Paradox in Endurance-Trained Athletes J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5755 - 5761. [Abstract] [Full Text] [PDF]

				D. S. Hardin, A. Leblanc, G. Marshall, and D. K. Seilheimer Mechanisms of insulin resistance in cystic fibrosis Am J Physiol Endocrinol Metab, November 1, 2001; 281(5): E1022 - E1028. [Abstract] [Full Text] [PDF]

				M. J. Toth, C. K. Sites, W. T. Cefalu, D. E. Matthews, and E. T. Poehlman Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women Am J Physiol Endocrinol Metab, July 1, 2001; 281(1): E113 - E121. [Abstract] [Full Text] [PDF]

				J. F. Youngren, S. Keen, J. L. Kulp, C. J. Tanner, J. A. Houmard, and I. D. Goldfine Enhanced muscle insulin receptor autophosphorylation with short-term aerobic exercise training Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E528 - E533. [Abstract] [Full Text] [PDF]

				D. Malkova, R. D. Evans, K. N. Frayn, S. M. Humphreys, P. R. M. Jones, and A. E. Hardman Prior exercise and postprandial substrate extraction across the human leg Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1020 - E1028. [Abstract] [Full Text] [PDF]

				M. Gaster, P. Poulsen, A. Handberg, H. D. Schroder, and H. Beck-Nielsen Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle Am J Physiol Endocrinol Metab, May 1, 2000; 278(5): E910 - E916. [Abstract] [Full Text] [PDF]

				M.-L. Liu, R. Bergholm, S. Makimattila, S. Lahdenpera, M. Valkonen, H. Hilden, H. Yki-Jarvinen, and M.-R. Taskinen A marathon run increases the susceptibility of LDL to oxidation in vitro and modifies plasma antioxidants Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1083 - E1091. [Abstract] [Full Text] [PDF]

				M. Pendergrass, E. Fazioni, D. Collins, and R. A. DeFronzo IGF-I increases forearm blood flow without increasing forearm glucose uptake Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E345 - E350. [Abstract] [Full Text] [PDF]

				P. J. Arciero, D. L. Smith, and J. Calles-Escandon Effects of short-term inactivity on glucose tolerance, energy expenditure, and blood flow in trained subjects J Appl Physiol, April 1, 1998; 84(4): 1365 - 1373. [Abstract] [Full Text] [PDF]

				D. S. Hardin, A. LeBlanc, S. Lukenbaugh, L. Para, and D. K. Seilheimer Proteolysis Associated With Insulin Resistance in Cystic Fibrosis Pediatrics, March 1, 1998; 101(3): 433 - 437. [Abstract] [Full Text] [PDF]

				A. Kennedy, T. W. Gettys, P. Watson, P. Wallace, E. Ganaway, Q. Pan, and W. T. Garvey The Metabolic Significance of Leptin in Humans: Gender-Based Differences in Relationship to Adiposity, Insulin Sensitivity, and Energy Expenditure J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1293 - 1300. [Abstract] [Full Text] [PDF]