Exercise and Insulin Sensitivity: A Review

Physical activity has a beneficial effect on insulin sensitivity in normal as well as insulin resistant populations. A distinction should be made between the acute effects of exercise and genuine training effects. Up to two hours after exercise, glucose uptake is in part elevated due to insulin independent mechanisms, probably involving a contraction-induced increase in the amount of GLUT4 associated with the plasma membrane and T-tubules. However, a single bout of exercise can increase insulin sensitivity for at least 16 h post exercise in healthy as well as NIDDM subjects. Recent studies have accordingly shown that acute exercise also enhances insulin stimulated GLUT4 translocation. Increases in muscle GLUT4 protein content contribute to this effect, and in adddition it has been hypothesized that the depletion of muscle glycogen stores with exercise plays a role herein. Physical training potentiates the effect of exercise on insulin sensitivity through multiple adaptations in glucose transport and metabolism. In addition, training may elicit favourable changes in lipid metabolism and can bring about improvements in the regulation of hepatic glucose output, which is especially relevant to NIDDM. It is concluded that physical training can be considered to play an important, if not essential role in the treatment and prevention of insulin insensitivity.

Key words:

Skeletal muscle - GLUT4 - diabetes - insulin resistance - physical training

References

• 1 Allenberg K, Johansen K, Saltin B. Skeletal muscle adaptations to physical training in type II (non-insulin-dependent) diabetes mellitus.  Acta Med Scand. 1988;  223 365-373
• 2 Andersen P, Henriksson J. Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise.  J Physiol Lond. 1977;  270 677-690
• 3 Bangsbo J, Gollnick P D, Graham T E, Juel C, Kiens B, Mizuno M, Saltin B. Anaerobic energy production and O₂ deficit-debt relationship during exhaustive exercise in humans.  J Physiol Lond. 1990;  422 539-559
• 4 Bjorkman O. Fuel metabolism during exercise in normal and diabetic man.  Diabetes Metab Rev. 1986;  1 319-357
• 5 Bjornholm M, Kawano Y, Lehtihet M, Zierath J R. Insulin receptor substrate-1 phosphorylation and phosphatidylinositol 3-kinase activity in skeletal muscle from NIDDM subjects after in vivo insulin stimulation.  Diabetes. 1997;  46 524-527
• 6 Bjorntorp P. Metabolic implications of body fat distribution.  Diabetes Care. 1991;  14 1132-1143
• 7 Bjorntorp P, Fahlen M, Grimby G, Gustafson A, Holm J, Renstrom P, Schersten T. Carbohydrate and lipid metabolism in middle-aged, physically well-trained men.  Metabolism. 1972;  21 1037-1044
• 8 Bjorntorp P, Sjostrom L. Carbohydrate storage in man: speculations and some quantitative considerations.  Metabolism. 1978;  27 1853-1865
• 9 Bloch G, Chase J R, Meyer D B, Avison M J, Shulman G I, Shulman R G. In vivo regulation of rat muscle glycogen resynthesis after intense exercise.  Am J Physiol. 1994;  266 91
• 10 Bogardus C, Ravussin E, Robbins D C, Wolfe R R, Horton E S, Sims E A. Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus.  Diabetes. 1984;  33 311-318
• 11 Bogardus C, Thuillez P, Ravussin E, Vasquez B, Narimiga M, Azhar S. Effect of muscle glycogen depletion on in vivo insulin action in man.  J Clin Invest. 1983;  72 1605-1610
• 12 Bonen A, Tan M H, Clune P, Kirby R L. Effects of exercise on insulin binding to human muscle.  Am J Physiol. 1985;  248 408
• 13 Bourey R E, Coggan A R, Kohrt W M, Kirwan J P, King D S, Holoszy J O. Effect of exercise on glucose disposal: response to a maximal insulin stimulus.  J Appl Physiol. 1990;  69 1689-1694
• 14 Braun B, Zimmermann M B, Kretchmer N. Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitus.  J Appl Physiol. 1995;  78 300-306
• 15 Burstein R, Polychronakos C, Toews C J, MacDougall J D, Guyda H J, Posner B I. Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes.  Diabetes. 1985;  34 756-760
• 16 Clauser E, Leconte I, Auzan C. Molecular basis of insulin resistance.  Horm Res. 1992;  38 5-12
• 17 Coderre L, Kandror K V, Vallega G, Pilch P F. Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle.  J Biol Chem. 1995;  270 27584-27588
• 18 Coggan A R, Swanson S C, Mendenhall L A, Habash D L, Kien C L. Effect of endurance training on hepatic glycogenolysis and gluconeogenesis during prolonged exercise in men.  Am J Physiol. 1995;  268 383
• 19 Colberg S R, Hagberg J M, McCole S D, Zmuda J M, Thompson P D, Kelley D E. Utilization of glycogen but not plasma glucose is reduced in individuals with NIDDM during mild-intensity exercise.  J Appl Physiol. 1996;  81 2027-2033
• 20 Colberg S R, Simoneau J A, Thaete F L, Kelley D E. Skeletal muscle utilization of free fatty acids in women with visceral obesity (see comments).  J Clin Invest. 1995;  95 1846-1853
• 21 Consoli A. Role of liver in pathophysiology of NIDDM.  Diabetes Care. 1992;  15 430-441
• 22 Davis R J. The mitogen-activated protein kinase signal transduction pathway.  J Biol Chem. 1993;  268 14553-14556
• 23 DeFronzo R A, Ferrannini E, Hendler R, Wahren J, Felig P. Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange.  Prof Natl Acad Sci USA. 1978;  75 5173-5177
• 24 DeFronzo R A, Jacot E, Jequier E, Maeder E, Wahren J, Felber J P. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization.  Diabetes. 1981;  30 1000-1007
• 25 DeFronzo R A, Sherwin R S, Kraemer N. Effect of physical training on insulin action in obesity.  Diabetes. 1987;  36 1379-1385
• 26 DeFronzo R A, Tobin J D, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.  Am J Physiol. 1979;  237 223
• 27 Dela F, Larsen J J, Mikines K J, Ploug T, Petersen L N, Galbo H. Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training.  Diabetes. 1995;  44 1010-1020
• 28 Dela F, Mikines K J, von Linstow M, Secher N H, Galbo H. Effect of training on insulin-mediated glucose uptake in human muscle.  Am J Physiol. 1992;  263 1143
• 29 Dela F, Ploug T, Handberg A, Petersen L N, Larsen J J, Mikines K J, Galbo H. Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM.  Diabetes. 1994;  43 862-865
• 30 Despres J-P. Visceral obesity, insulin resistance, and dyslipidemia: contribution of endurance exercise training to the treatment of the plurimetabolic syndrome.  Exerc Sport Sci Ref. 1997;  25 271-300
• 31 Despres J P, Pouliot M C, Moorjani S, Nadeau A, Tremblay A, Lupien P J, Theriault G, Bouchard C. Loss of abdominal fat and metabolic response to exercise training in obese women.  Am J Physiol. 1991;  261 167
• 32 Devlin J T, Hirshman M, Horton E D, Horton E S. Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise.  Diabetes. 1987;  36 434-439
• 33 Devlin J T, Horton E S. Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men.  Diabetes. 1985;  34 973-979
• 34 Eriksson K F, Lindgarde F. Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study.  Diabetologia. 1991;  34 891-898
• 35 Eriksson K F, Saltin B, Lindgarde F. Increased skeletal muscle capillary density precedes diabetes development in men with impaired glucose tolerance. A 15-year follow-up.  Diabetes. 1994;  43 805-808
• 36 Etgen Jr G J, Jensen J, Wilson C M, Hunt D G, Cushman S W, Ivy J L. Exercise training reverses insulin resistance in muscle by enhanced recruitment of GLUT-4 to the cell surface.  Am J Physiol. 1997;  272 869
• 37 Felig P, Cherif A, Minagawa A, Wahren J. Hypoglycemia during prolonged exercise in normal men.  N Engl J Med. 1982;  306 895-900
• 38 Ferrannini E, Wahren J, Felig P, DeFronzo R A. The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man.  Metabolism. 1980;  29 28-35
• 39 Goodyear L J, Chang P Y, Sherwood D J, Dufresne S D, Moller D E. Effects of exercise and insulin on mitogen-activated protein kinase signalling pathways in rat skeletal muscle.  Am J Physiol. 1996;  271 408
• 40 Goodyear L J, Giorgino F, Sherman L A, Carey J, Smith R J, Dohm G L. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects.  J Clin Invest. 1995;  95 2195-2204
• 41 Goodyear L J, Hirshman M F, King P A, Horton E D, Thompson C M, Horton E S. Skeletal muscle plasma membrane glucose transport and glucose transporters after exercise.  J Appl Physiol. 1990;  68 193-198
• 42 Goodyear L J, Hirshman M F, Smith R J, Horton E S. Glucose transporter number, activity, and isoform content in plasma membranes of red and white skeletal muscle.  Am J Physiol. 1991;  261 561
• 43 Goodyear L J, King P A, Hirshman M F, Thompson C M, Horton E D, Horton E S. Contractile activity increases plasma membrane glucose transporters in absence of insulin.  Am J Physiol. 1990;  258 672
• 44 Groop L C, Bonadonna R C, DelPrato S, Ratheiser K, Zyck K, Ferrannini E, DeFronzo R A. Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance.  J Clin Invest. 1989;  84 205-213
• 45 Gulve E A, Ren J M, Marshall B A, Gao J, Hansen P A, Holloszy J O, Mueckler M. Glucose transport activity in skeletal muscles from transgenic mice overexpressing GLUT1. Increased basal transport is associated with a defective response to diverse stimuli that activate GLUT4.  J Biol Chem. 1994;  269 18366-18370
• 46 Gulve E A, Spina R J. Effect of 7 - 10 days of cycle ergometer exercise on skeletal muscle GLUT-4 protein content.  J Appl Physiol. 1995;  79 1562-1566
• 47 Hansen P A, Nolte L A, Chen M M, Holloszy J O. Increased GLUT-4 translocation mediates enhanced insulin sensitivity of muscle glucose transport after exercise.  J Appl Physiol. 1998;  85 1218-1222
• 48 Hardin D S, Azzarelli B, Edwards J, Wigglesworth J, Maianu L, Brechtel G, Johnson A, Baron A, Garvey W T. Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT 4 in skeletal muscles.  J Clin Endocrionol Metab. 1995;  80 2437-2446
• 49 Hargreaves M, Kiens B, Richter E A. Effect of increased plasma free fatty acid concentrations on muscle metabolism in exercising men.  J Appl Physiol. 1991;  70 194-201
• 50 Heath G W, Gavin J Rd, Hinderliter J M, Hagberg J M, Bloomfield S A, Holloszy J O. Effects of exercise and lack of exercise on glucose tolerance and insulin sensitivity.  J Appl Physiol. 1983;  55 512-517
• 51 Helmrich S P, Ragland D R, Leung R W, Paffenbarger Jr R S. Physical activity and reduced occurrence on non-insulin-dependent diabetes mellitus (see comments).  N Engl J Med. 1991;  325 147-152
• 52 Henriksen E J, Bourey R E, Rodnick K J, Koranyi L, Permutt M A, Holloszy J O. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles.  Am J Physiol. 1990;  259 598
• 53 Holloszy J O, Coyle E F. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences.  J Appl Physiol. 1984;  56 831-838
• 54 Holloszy J O, Schultz J, Kusnierkiewicz J, Hagberg J M, Ehsani A A. Effects of exercise on glucose tolerance and insulin resistance. Brief review and some preliminary results.  Acta Med Scand Suppl. 1986;  711 55-65
• 55 Houmard J A, Hickey M S, Tyndall G L, Gavigan K E, Dohm G L. Seven days of exercise increase GLUT-4 protein content in human skeletal muscle.  J Appl Physiol. 1995;  79 1936-1938
• 56 Houmard J A, Shinebarger M H, Dolan P L, Leggett Frazier N, Bruner R K, McCammon M R, Israel R G, Dohm G L. Exercise training increases GLUT-4 protein concentration in previously sedentary middle-aged men.  Am J Physiol. 1993;  264 901
• 57 Hughes V A, Fiatarone M A, Fielding R A, Kahn B B, Ferrara C M, Shepherd P, Fisher E C, Wolfe R R, Elahi D, Evans W J. Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance.  Am J Physiol. 1993;  264 862
• 58 Ivy J L, Kuo C H. Regulation of GLUT4 protein and glycogen synthase during muscle glycogen synthesis after exercise.  Acta Physiol Scand. 1998;  162 295-304
• 59 James D E, Kraegen E W, Chisholm D J. Effects of exercise training on in vivo insulin action in individual tissues of the rat.  J Clin Invest. 1985;  76 657-666
• 60 Kahn C R. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes.  Diabetes. 1994;  43 1066-1084
• 61 Kahn S E, Larson V G, Beard J C, Cain K C, Fellingham G W, Schwartz R S, Veith R C, Stratton J R, Cerqueira M D, Abrass I B. Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging.  Am J Physiol. 1990;  258 943
• 62 Kang J, Robertson R J, Hagberg J M, Kelley D E, Goss F L, DaSilva S G, Suminski R R, Utter A C. Effect of exercise intensity on glucose and insulin metabolism in obese individuals and obese NIDDM patients.  Diabetes Care. 1996;  19 341-349
• 63 Kelley D E, Mandarino L J. Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus.  J Clin Invest. 1990;  86 1999-2007
• 64 Kelley D E, Mintun M A, Watkins S C, Simoneau J A, Jadali F, Fredrickson A, Beattie J, Theriault R. The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle.  J Clin Invest. 1996;  97 2705-2713
• 65 Kelley D E, Simoneau J A. Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus.  J Clin Invest. 1994;  94 2349-2356
• 66 Kim Y, Inoue T, Nakajima R, Nakae K, Tamura T, Tokuyama K, Suzuki M. Effects of endurance training on gene expression of insulin signal transduction pathway.  Biochem Biophys Res Commun. 1995;  210 766-773
• 67 King D S, Dalsky G P, Staten M A, Clutter W E, Van Houten D R, Holloszy J O. Insulin action and secretion in endurance-trained and untrained humans.  J Appl Physiol. 1987;  63 2247-2252
• 68 King P A, Betts J J, Horton E D, Horton E S. Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle.  Am J Physiol. 1993;  265 452
• 69 King P A, Horton E D, Hirshman M F, Horton E S. Insulin resistance in obese Zucker rat (fa/fa) skeletal muscle is associated with a failure of glucose transporter translocation.  J Clin Invest. 1992;  90 1568-1575
• 70 Kjaer M. Hepatic glucose production during exercise. In: Richter EA (ed) Skeletal muscle metabolism in exercise and diabetes. New York; Plenum Press 1998: 117-127
• 71 Kochan R G, Lamb D R, Lutz S A, Perrill C V, Reimann E M, Schlender K K. Glycogen synthase activation in human skeletal muscle: effects of diet and exercise.  Am J Physiol. 1979;  236 666
• 72 Kohrt W M, Kirwan J P, Staten M A, Bourey R E, King D S, Holloszy J O. Insulin resistance in aging is related to abdominal obesity.  Diabetes. 1993;  42 273-281
• 73 Kristiansen S, Hargreaves M, Richter E A. Exercise-induced increase in glucose transport, GLUT-4, and VAMP-2 in plasma membrane from human muscle.  Am J Physiol. 1996;  270 201
• 74 Krotkiewski M, Bjorntorp P. Mucsle tissue in obesity with different distribution of adipose tissue. Effects of physical training.  Int J Obes. 1986;  10 331-341
• 75 Krotkiewski M, Lonnroth P, Mandroukas K, Wroblewski Z, Rebuffe Scrive M, Holm G, Smith U, Bjorntorp P. The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and type 2 (non-insulin-dependent) diabetes mellitus.  Diabetologia. 1985;  28 881-890
• 76 Lavoie J M, Bongbele J, Cardin S, Belisle M, Terrettaz J, Van de Werve G. Increased insulin suppression of plasma free fatty acid concentration in exercise-trained rats.  J Appl Physiol. 1993;  74 293-296
• 77 Lemon P W, Nagle F J. Effects of exercise on protein and amino acid metabolism.  Med Sci Sports Exerc. 1981;  13 141-149
• 78 Li W M, McNeill J H. Quantitative methods for measuring the insulin-regulatable glucose transporter (Glut4).  J Pharmacol Toxicol Methods. 1997;  38 1-10
• 79 Lohmann D, Liebold F, Heilmann W, Senger H, Pohl A. Diminished insulin response in highly trained athletes.  Metabolism. 1978;  27 521-524
• 80 Lund S, Vestergaard H, Andersen P H, Schmitz O, Gotzsche L B, Pedersen O. GLUT-4 content in plasma membrane of muscle from patients with non-insulin-dependent diabetes mellitus.  Am J Physol. 1993;  265 897
• 81 Maehlum S, Felig P, Wahren J. Splanchnic glucose and muscle glycogen metabolism after glucose feeding during postexercise recovery.  Am J Physiol. 1978;  235 260
• 82 Manson J E, Rimm E B, Stampfer M J, Colditz G A, Willett W C, Krolewski A S, Rosner B, Hennekens C H, Speizer F E. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women.  Lancet. 1991;  338 774-778
• 83 Marin P, Andersson B, Krotkiewski M, Bjorntorp P. Muscle fiber composition and capillary density in women and men with NIDDM.  Diabetes Care. 1994;  17 382-386
• 84 Marin P, Rebuffe Scrive M, Smith U, Bjorntorp P. Glucose uptake in human adipose tissue.  Metabolism. 1987;  36 1154-1160
• 85 Marshall S, Garvey W T, Traxinger R R. New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids.  Faseb J. 1991;  5 3031-3036
• 86 Martin I K, Katz A, Wahren J. Splanchnic and muscle metabolism during exercise in NIDDM patients.  Am J Physiol. 1995;  269 590
• 87 Mauriege P, Prud'Homme D, Marcotte M, Yoshioka M, Tremblay A, Despres J P. Regional differences in adipose tissue metabolism between sedentary and endurance-trained women.  Am J Physiol. 1997;  273 506
• 88 McCoy M, Proietto J, Hargreaves M. Effect of detraining on GLUT-4 protein in human skeletal muscle.  J Appl Physiol. 1994;  77 1532-1536
• 89 Mikines K J, Sonne B, Farrell P A, Tronier B, Galbo H. Effect of physical exercise on sensitivity and responsiveness to insulin in humans.  Am J Physiol. 1988;  254 259
• 90 Mikines K J, Sonne B, Farrell P A, Tronier B, Galbo H. Effect of training on the dose-response relationship for insulin action in men.  J Appl Physiol. 1989;  66 695-703
• 91 Mikines K J, Sonne B, Tronier B, Galbo H. Effects of acute exercise and detraining on insulin action in trained men.  J Appl Physiol. 1989;  66 704-711
• 92 Mikines K J, Sonne B, Tronier B, Galbo H. Effects of training and detraining on dose-response relationship between glucose and insulin secretion.  Am J Physiol. 1989;  256 596
• 93 Miller J P, Pratley R E, Goldberg A P, Gordon P, Rubin M, Treuth M S, Ryan A S, Hurley B F. Strength training increases insulin action in healthy 50- to 65-yr-old men.  J Appl Physiol. 1994;  77 1122-1127
• 94 Minuk H L, Vranic M, Marliss E B, Hanna A K, Albisser A M, Zinman B. Glucoregulatory and metabolic response to exercise in obese noninsulin-dependent diabetes.  Am J Physiol. 1981;  240 464
• 95 Ploug T, Galbo H, Vinten J, Jorgensen M, Richter E. Kinetics of glucose transport in rat muscle: effects of insulin and contractions.  Am J Physiol. 1987;  253 20
• 96 Price T B, Perseghin G, Duleba A, Chen W, Chase J, Rothman D L, Shulman R G, Shulman G I. NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise.  Proc Natl Acad Sci USA. 1996;  93 5329-5334
• 97 Ren J M, Marshall B A, Gulve E A, Gao J, Johnson D W, Holloszy J O, Mueckler M. Evidence from transgenic mice that glucose transport is rate-limiting for glycogen deposition and glycolysis in skeletal muscle.  J Biol Chem. 1993;  268 16113-16115
• 98 Ren J M, Semenkovich C F, Gulve E A, Gao J, Holloszy J O. Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle.  J Biol Chem. 1994;  269 14396-14401
• 99 Revers R R, Fink R, Griffin J, Olefsky J M, Kolterman O G. Influence of hyperglycemia on insulin's in vivo effects in type II diabetes.  J Clin Invest. 1984;  73 664-672
• 100 Richter E A, Mikines K J, Galbo H, Kiens B. Effect of exercise on insulin action in human skeletal muscle.  J Appl Physiol. 1989;  66 876-885
• 101 Richter E A, Ploug T, Galbo H. Increased muscle glucose uptake after exercise. No need for insulin during exercise.  Diabetes. 1985;  34 1041-1048
• 102 Robinson K A, Sens D A, Buse M G. Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor (published erratum appears in Diabetes 1993 Oct; 42(10):1547).  Diabetes. 1993;  42 1333-1346
• 103 Romijn J A, Coyle E F, Sidossis L S, Gastaldelli A, Horowitz J F, Endert E, Wolfe R R. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.  Am J Physiol. 1993;  265 391
• 104 Roy D, Marette A. Exercise induces the translocation of GLUT4 to transverse tubules from an intracellular pool in rat skeletal muscle.  Biochem Biophys Res Commun. 1996;  223 147-152
• 105 Ruderman N B, Ganda O P, Johansen K. The effect of physical training on glucose tolerance and plasma lipids in maturity-onset diabetes.  Diabetes. 1979;  28 89-92
• 106 Saloranta C, Koivisto V, Widen E, Falholt K, DeFronzo R A, Harkonen M, Groop L. Contribution of muscle and liver to glucose-fatty acid cycle in humans.  Am J Physiol. 1993;  264 605
• 107 Saltin B, Lindgarde F, Houston M, Horlin R, Nygaard E, Grad P. Physical training and glucose tolerance in middle-aged men with chemical diabetes.  Diabetes. 1979;  28 30-32
• 108 Scheck S H, Barnard R J, Lawani L O, Youngren J F, Martin D A, Singh R. Effects of NIDDM on the glucose transport system in human skeletal muscle.  Diabetes Res. 1991;  16 111-119
• 109 Scheen A J, Lefebvre P J. Assessment of insulin resistance in vivo: application to the study of type 2 diabetes.  Horm Res. 1992;  38 19-27
• 110 Schneider S H, Amorosa L F, Khachadurian A K, Ruderman N B. Studies on the mechanism of improved glucose control during regular exercise in type 2 (non-insulin-dependent) diabetes.  Diabetologia. 1984;  26 355-360
• 111 Seals D R, Hagberg J M, Allen W K, Hurley B F, Dalsky G P, Ehsani A A, Holloszy J O. Glucose tolerance in young and older athletes and sedentary men.  J Appl Physiol. 1984;  56 1521-1525
• 112 Seals D R, Hagberg J M, Hurley B F, Ehsani A A, Holloszy J O. Effects of endurance training on glucose tolerance and plasma lipid levels in older men and women.  J Am Med Ass. 1984;  252 645-649
• 113 Simoneau J A, Kelley D E. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM.  J Appl Physiol. 1997;  83 166-171
• 114 Soman V R, Koivisto V A, Deibert D, Felig P, DeFronzo R A. Increased insulin sensitivity and insulin binding to monocytes after physical training.  N Engl J Med. 1979;  301 1200-1204
• 115 Suda K, Izawa T, Komabayashi T, Tsuboi M, Era S. Effect of insulin on adipocyte lipolysis in exercise-trained rats.  J Appl Physiol. 1993;  74 2935-2939
• 116 Sushruta S. . Varanasi; Vidya Vilas Press 1963: 361-387
• 117 Taskinen M R, Bogardus C, Kennedy A, Howard B V. Multiple disturbances of free fatty acid metabolism in noninsulin-dependent diabetes. Effect of oral hypoglycemic therapy.  J Clin Invest. 1985;  76 637-644
• 118 Tonino R P. Effect of physical training on the insulin resistance of aging.  Am J Physiol. 1989;  256 356
• 119 Treadway J L, James D E, Burcel E, Ruderman N B. Effect of exercise on insulin receptor binding and kinase activity in skeletal muscle.  Am J Physiol. 1989;  256 144
• 120 Trovati M, Carta Q, Cavalot F, Vitali S, Banaudi C, Lucchina P G, Fiocchi F, Emanuelli G, Lenti G. Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients.  Diabetes Care. 1984;  7 416-420
• 121 Vestergaard H, Andersen P H, Lund S, Schmitz O, Junker S, Pedersen O. Pre- and posttranslational upregulation of muscle-specific glycogen synthase in athletes.  Am J Physiol. 1994;  266 101
• 122 Vukovich M D, Arciero P J, Kohrt W M, Racette S B, Hansen P A, Holloszy J O. Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners.  J Appl Physiol. 1996;  80 240-244
• 123 Vusse vd G J, Reneman R S. Lipid metabolism in muscle. In: Rowell BR, Sheperd JT (eds) Exercise: regulation and integration of multiple systems. Oxford; Oxford University Press 1996: 953-994
• 124 Wallberg Henriksson H, Constable S H, Young D A, Holloszy J O. Glucose transport into rat skeletal muscle: interaction between exercise and insulin.  J Appl Physiol. 1988;  65 909-913
• 125 Wojtaszewski J F, Hansen B F, Kiens B, Richter E A. Insulin signaling in human skeletal muscle: time course and effect of exercise.  Diabetes. 1997;  46 1775-1781
• 126 Yamanouchi K, Shinozaki T, Chikada K, Nishikawa T, Ito K, Shimizu S, Ozawa N, Suzuki Y, Maeno H, Kato K. Daily walking combined with diet therapy is a useful means for obese NIDDM patients not only to reduce body weight but also to improve insulin sensitivity.  Diabetes Care. 1995;  18 775-778
• 127 Yki Jarvinen H, Daniels M C, Virkamaki A, Makimattila S, DeFronzo R A, McClain D. Increased glutamine: fructose-6-phosphate amidotransferase activity in skeletal muscle of patients with NIDDM.  Diabetes. 1996;  45 302-307
• 128 Young D A, Wallberg Henriksson H, Sleeper M D, Holloszy J O. Reversal of the exercise-induced increase in muscle permeability to glucose.  Am J Physiol. 1987;  253 335
• 129 Young J C, Enslin J, Kuca B. Exercise intensity and glucose tolerance in trained and nontrained subjects.  J Appl Physiol. 1989;  67 39-43
• 130 Zhou Q, Dohm G L. Treadmill running increases phosphatidylinostol 3-kinase activity in rat skeletal muscle.  Biochem Biophys Res Commun. 1997;  236 647-650