By: Eric Cressey
All too often, we overlook the important underlying anatomy and physiology upon which solid training and nutrition recommendations are based. In rushing to get to the “meat and potatoes” (the program or ultimate recommendations) of an article, we fail to truly question and understand the basis for why we do what we do. Take, for example, post-workout nutrition. Ever wonder why you can suck up ridiculous amounts of high-carb foods after you train? In the Rugged mission statement, we promised to make you think; the following article should do just that. And, if it doesn’t, you can at least gain an appreciation for one facet of an Exercise Science graduate student’s course of study. Without further ado, I present “the insulin response to exercise: carbohydrate, fat, and protein metabolism implications.”
Insulin is well recognized as a powerful hormone capable of diverse metabolic effects in a variety of scenarios. Perhaps the most noteworthy of these scenarios is exercise, the stress of which presents significant metabolic demands. The response of insulin to these demands has far-reaching implications in terms of carbohydrate, fat, and protein metabolism.
Insulin: Broad Roles in Carbohydrate, Fat, and Protein Metabolism
Insulin exerts its most pronounced effects on carbohydrate metabolism at the skeletal muscle and hepatic levels. The hormone facilitates uptake of glucose into skeletal muscle and the liver, thus promoting glycogenesis. Simultaneously, it inhibits hepatic glucose release (glycogenolysis) and production (gluconeogenesis) (1). Insulin appears to demonstrate its most immediate and powerful influence in suppressing glycogenolysis, as more insulin is required to inhibit gluconeogenesis than glycogenolysis in non-diabetic subjects (2).
Insulin also plays crucial roles in fat metabolism, regulating both lipolysis and lipogenesis. Lipolysis, the hydrolysis of triglycerides, is a requisite step in fat oxidation, as it liberates fatty acids for transport to mitochondria for oxidation (3). Numerous studies have demonstrated that insulin markedly blunts lipolysis at rest (3-5). Likewise, via facilitation of glucose uptake in liver and adipose tissue, insulin stimulates lipogenesis as well. Glycolytic conversion of glucose to acetyl-CoA is the precursor to fatty acid synthesis (1,6).
In terms of protein metabolism, insulin’s foremost role is inhibition of protein breakdown. Although the hormone does play a role in promoting protein synthesis, this effect is largely dependent on amino acid availability (7-9). Some studies have noted that insulin elevations without concurrent increases in amino acid availability actually decrease protein synthesis as a result of low plasma amino acid concentrations (10,11). Conversely, dietary amino acids exert their most prominent effect on optimizing protein synthesis rather than reducing protein breakdown (7,8,12).
Hormonal Regulation of Blood Glucose: Carbohydrate, Fat, and Protein Metabolism
Maintenance of plasma glucose concentrations is of paramount importance to optimal functioning of muscles and the central nervous system. Blood glucose regulation involves interactions of carbohydrate, fat, and protein metabolism; these interactions are even more readily apparent during exercise. While insulin is certainly a powerful modulator of plasma glucose levels, one must also consider several other hormones that exert the opposite physiological effects as insulin. Knowledge of these hormones - glucagon, growth hormone, cortisol, and the catecholamines epinephrine and norepinephrine - is an important prerequisite to comprehending the insulin response to exercise.
Glucagon responds to the same stimuli as insulin, but has the exact opposite effects on blood glucose concentrations. These effects are, on the whole, catabolic and anti-anabolic. They include stimulation of glycogenolysis, gluconeogenesis, and protein degradation with concurrent inhibition of protein synthesis (13,14). Some studies have noted that glucagon has a stimulatory effect on lipolysis in human adipose tissue in vitro, and pharmacological interventions to induce dramatic hyperglucagonemia have proven sufficient to stimulate lipolysis (15-17). However, there is insufficient evidence to suggest that normal human hyperglucagonemia can directly induce lipolysis in vivo (18,19). While hypoglycemia is the most potent stimuli for glucagon release from the pancreas, high concentrations of insulin during hypoglycemia can suppress the glucagon response (20).
Growth hormone serves as a counter-regulatory hormone to insulin in carbohydrate and fat metabolism, but works synergistically with insulin in establishing an anabolic protein metabolism environment (21). Growth hormone’s insulin-antagonistic effects include increased lipolysis, decreased tissue glucose uptake, and enhanced hepatic gluconeogenesis (22-24). Meanwhile, growth hormone has an anabolic effect via enhanced protein synthesis and retention (25-31).
Cortisol opposes insulin action in several regards. This glucocorticoid is likely most well known for its catabolic properties, which include stimulation of lipolysis in adipose tissue, protein degradation (the hormone also inhibits protein synthesis), and hepatic gluconeogenesis (32-35). Additionally, in terms of insulin resistance, cortisol not only directly inhibits glucose entry to cells, but also delays insulin action via a post-insulin receptor block (33,36).
The catecholamines epinephrine and norepinephrine work in opposition to insulin in the regulation of the plasma glucose concentration. Epinephrine provides a strong stimulus to hepatic glucose mobilization via glycogenolysis and gluconeogenesis (37), although there is a lower threshold for glycogenolysis to occur (38). The catecholamines also stimulate lipolysis in adipose tissue (33,39) and interfere with glucose clearance by insulin (40). While the catecholamines have a catabolic effect on both liver and skeletal muscle glycogen, there is considerable evidence that they have anti-catabolic effects on muscle protein (41-43).
Thyroxine is a less recognized regulator of plasma glucose concentrations. While the hormone itself has no direct effect on substrate mobilization at rest or during exercise, it does serve a permissive role for the hormones that are directly involved in plasma glucose regulation. Thyroxine acts by either increasing receptor quantity at the target tissues or by increasing receptor affinity for the aforementioned hormones; during exercise, these effects are more pronounced, as there is an increase in free thyroxine concentrations (33). Hypothyroidism (and the related thyroxine deficiency) has been shown to interfere with fuel mobilization (33).
Clearly, a discussion of insulin must include attention to several glucoregulatory hormones, each of which has significant implications in carbohydrate, fat, and protein metabolism. Figure 1 summarizes the roles of those hormones with a direct effect on fuel metabolism in the liver, skeletal muscle, and adipose tissue.
Glucoregulatory Hormone Response to Exercise
Insulin is the only glucoregulatory hormone that decreases with exercise under normal physiologic conditions (33). Galbo et al. (1975) found that insulin decreased both during prolonged treadmill running at 76%VO2max and with incremental treadmill exercise at 47% and 77% VO2max (no significant difference was noted at 100% VO2max) (44). Numerous other studies have observed similar decreases (45-47); these decreases are more prominent in longer duration exercise at lower intensities than in short duration, high intensity exercise (47).
As a hormone working in direct opposition to insulin, glucagon increases in response to exercise. This effect has been demonstrated in both incremental (44) and prolonged (44,45) endurance exercise. In the aforementioned study by Galbo et al. (1975), the investigators found that glucagon increased more in the longer duration scenario (threefold increase over the resting value) than in incremental exercise (an increase of 35% from rest to VO2max) (44). Others have also noted that glucagon’s effects are clearly more prominent in longer duration scenarios (48).
Describing plasma growth hormone changes during exercise proves to be a complex task, as numerous physical, psychological, chemical, and exercise modality (both aerobic and resistance training) factors. In a broad sense, plasma growth hormone concentrations increase as exercise intensity increases; plasma GH may increase 25-fold over resting concentrations at VO2max (49). In fact, recent research by Wideman et al. (2003) noted a linear relationship between GH secretion and exercise intensity (50). Bunt et al. (1986) found that plasma GH increased by 500-600% in both runners and non-runners (runners had a higher response) during one hour of treadmill running at 60% VO2max, implying a duration effect for GH secretion as well (33,51). The growth hormone response to resistance training is a product of the work-rest intervals, loads, and volume utilized, with one minute rest periods, 10-repetition maximums, and high volumes proving most beneficial in enhancing GH secretion (50,52).
Cortisol increases in response to exercise are related to intensity and duration. A study by Davies and Few (1973) demonstrated the presence of an intensity threshold that must be reached for cortisol increases to occur. In separate exercise sessions, subjects were tested for 60 minutes at 40%, 60%, 80%, and 100% VO2max. Plasma cortisol actually decreased at 40% VO2max over the course of the test, whereas cortisol increased whenever the intensity exceeded 60% VO2max (33). Apparently, light exercise facilitates plasma cortisol removal to the point that it exceeds secretion by the adrenal cortex in response to exercise. At greater intensities, secretion predominated over removal, which had increased even more (33). There also appears to be a duration threshold; Bonen (1973) observed that urinary excretion of cortisol did not change with 10 minutes of exercise at 76% VO2max. However, when the duration increased to 30 minutes, this excretion value doubled (53), likely due to a lag time in the hypothalamic-pituitary-adrenal axis between ACTH and cortisol secretion (54).
Numerous studies have found that epinephrine and norepinephrine secretions increase as exercise intensity increases (55-58). However, Kraemer et al. (1985) found that graded exercise did not increase plasma epinephrine above baseline at 54% VO2 max, implying an intensity threshold for catecholamine secretion (59). Several investigators have observed increasing plasma catecholamine concentrations as exercise duration increased (60,61). Galbo et al. (1975) demonstrated that intensity is more influential than duration in the catecholamine response to exercise, as plasma epinephrine increased steadily with prolonged treadmill exercise to exhaustion at 76% VO2 max, but graded exercise in the same subjects at 44, 77, and 100% of VO2 max yielded greater increases (55).
Glucose Uptake and Transport during Exercise
During exercise, muscle glucose uptake may increase 30-50 fold over resting values (62). There is only a limited supply of muscle glycogen, and it can virtually be depleted with just one hour of exercise at 70-75% VO2max (63); therefore, it is of no surprise that muscle glucose uptake increases so dramatically. Given insulin’s key role in promoting glucose uptake in skeletal muscle, it seems counterintuitive that the hormone would actually decrease with exercise. However, numerous physiological factors interact to ensure that plasma glucose is maintained while skeletal muscles receive adequate fuel for the continuation of exercise.
First, and perhaps most logically, muscular contractions promote blood flow to skeletal muscles. With blood flow comes more glucose and insulin, so in spite of the fact that insulin is actually decreasing, there is still more opportunity for glucose uptake than at rest (33,64). Meanwhile, a gradient for more rapid glucose diffusion into the cell via increased membrane permeability is created because the muscles are utilizing glucose at a faster rate (64,65). Like insulin, exercise also leads to glucose transporter changes at the sarcolemmal level. In both scenarios, membrane transport capability increases due to translocation of insulin-stimulated GLUT4 transporters to the sarcolemma and transverse tubules from intracellular sites (65-69).
Kennedy et al. (1999) demonstrated that 45-60 minutes of bicycling at 60-75% VO2max resulted in acute mean increases of 71-74% in sarcolemmal GLUT4 content in both normal and type 2 diabetic subjects (70). Others have verified this increase in plasma membrane GLUT4 content with exercise (71-73). The mechanism by which muscle contraction facilitates GLUT4 translocation to the plasma membrane is yet to be definitively elucidated; however, the most likely answer is high intramuscular calcium concentrations during exercise. More specifically, protein kinase C (PKC) is an intermediary that is dependent on calcium; PKC downregulation has been associated with reduced contraction-induced glucose transport (33,73). Potential autocrine and paracrine effects on contraction-stimulated glucose transport have also been suggested (73). You can find a scheme of the potential factors influencing GLUT4 translocation in skeletal muscle here (Hayashi et al, Am J Physiol 1997).
For the sake of this discussion, it is important to note that insulin and muscular contraction facilitate glucose transport via different pathways, as Yeh et al. (1995) noted that it is possible to inhibit insulin action without inhibiting that of muscle contractions (74). Brozinick et al. (1992) validated this assertion with the observation that contraction-induced facilitated glucose transport is normal in insulin resistant muscle (75). GLUT4 and GLUT1 are two key glucose transporters found in skeletal muscle. Unlike GLUT4, which is responsive to insulin action, GLUT1 exerts its effects on glucose transport independent of insulin stimulation (69).
Henriksen et al. (1990) observed that GLUT4 protein concentration is closely associated with maximal glucose transport capability; it logically follows that the overall quantity of glucose transporters (both GLUT4 and GLUT1) in the plasma membrane during exercise is proportional to muscle GLUT4 content (76). However, there is evidence to suggest that GLUT4 transporters are more associated with fast-twitch oxidative-glycolytic fibers, while GLUT1 transporters are associated with slow-twitch oxidative fibers. Additionally, there is evidence to suggest that GLUT1 transporter increases are achieved through several weeks of endurance training, whereas GLUT4 transporters are more responsive to individual exercise bouts (77). Therefore, variations in fiber-type may interfere with this assumption (78).
Summarily, with more glucose transporters (both insulin-stimulated and non-insulin-stimulated) present due to both chronic and acute exercise adaptations, less insulin is necessary to have the same physiological effect. On a related note, Ivy (1997) asserted that increased concentrations of enzymes responsible for the phosphorylation, storage, and oxidation of glucose are also responsible for the improved insulin action (68).
Conclusions: Bringing it all Together
At first glance, it seems counterintuitive for insulin to decrease during exercise, a time when muscle glucose uptake increases rapidly. Upon further review, though, one can recognize that numerous hormonal and intracellular factors interact with this decrease to maintain plasma glucose concentrations, facilitate muscle glucose uptake, and effect appropriate changes in carbohydrate, fat, and protein metabolism.
As exercise progresses, skeletal muscle glycogen depletion occurs and the muscles must look to plasma glucose as a fuel source. Assuming no provision of exogenous carbohydrate during exercise, plasma glucose must come from hepatic gluconeogenesis or glycogenolysis. These physiological occurrences are stimulated by the presence of the glucagon, epinephrine, and norepinephrine at the onset of exercise, and growth hormone and cortisol as exercise duration increases (33). As counterregulators to insulin, these five hormones can only be present in sufficient quantities to elicit the desirable effects on plasma glucose maintenance if the plasma insulin concentration is low.
While the counterregulatory hormones take care of maintaining plasma glucose, there must be additional physiological adaptations to promote muscle glucose uptake in spite of the decrease in plasma insulin concentrations that occur with exercise. These exercise-induced physiological adaptations include increased skeletal muscle blood flow (and, in turn, glucose and insulin delivery), increased membrane permeability to glucose, translocation of GLUT4 proteins to the sarcolemma and transverse tubules, and increased cellular concentrations of key enzymes involved in glucose utilization. While both insulin and exercise favorably influence glucose uptake, they do so by different pathways. Nonetheless, the positive effects of acute and chronic exercise on insulin action and both insulin-dependent and non-insulin-dependent glucose transporters are undeniable.
It is important to also note that glucagon, growth hormone, cortisol, and the catecholamines have effects that extend beyond plasma glucose regulation. All five hormones promote lipolysis, and thus serve as powerful regulators of fat metabolism (which is also dependent on insulin-related lipogenesis). This increased lipolysis favors the increased reliance on free fatty acids with longer durations, lower intensities, and situations of muscle glycogen depletion (79-82). Likewise, some of these hormones - glucagon, the catecholamines, and most notably, cortisol - continue to oppose insulin in protein metabolism by promoting proteolysis and inhibiting protein synthesis. Meanwhile, growth hormone works synergistically with insulin (and amino acids) to achieve an anabolic effect of elevated protein synthesis and decreased protein breakdown.
2. Adkins A, Basu R, Persson M, Dicke B, Shah P, Vella A, Schwenk WF, Rizza R. Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans. Diabetes. 2003 Sep;52(9):2213-20.
3. Horowitz JF, Mora-Rodriguez R, Byerley LO, Coyle EF. Lipolytic suppression following carbohydrate ingestion limits fat oxidation during exercise. Am J Physiol. 1997 Oct;273(4 Pt 1):E768-75.
4. Bonadonna RC, Groop LC, Zych K, Shank M, DeFronzo RA. Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans. Am J Physiol. 1990 Nov;259(5 Pt 1):E736-50.
5. Campbell PJ, Carlson MG, Hill JO, Nurjhan N. Regulation of free fatty acid metabolism by insulin in humans: role of lipolysis and reesterification. Am J Physiol. 1992 Dec;263(6 Pt 1):E1063-9.
6. Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep. 2001 Apr;2(4):282-6.
7.Castellino P, Luzi L, Simonson DC, Haymond M, DeFronzo RA. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Role of substrate availability on estimates of whole body protein synthesis. J Clin Invest. 1987 Dec;80(6):1784-93.
8.Tessari P, Inchiostro S, Biolo G, Trevisan R, Fantin G, Marescotti MC, Iori E, Tiengo A, Crepaldi G. Differential effects of hyperinsulinemia and hyperaminoacidemia on leucine-carbon metabolism in vivo. Evidence for distinct mechanisms in regulation of net amino acid deposition. J Clin Invest. 1987 Apr;79(4):1062-9.
9. Heslin MJ, Newman E, Wolf RF, Pisters PW, Brennan MF. Effect of hyperinsulinemia on whole body and skeletal muscle leucine carbon kinetics in humans. Am J Physiol. 1992 Jun;262(6 Pt 1):E911-8.
10. McNurlan MA, Garlick PJ. Influence of nutrient intake on protein turnover. Diabetes Metab Rev. 1989 Mar;5(2):165-89.
11. Frexes-Steed M, Lacy DB, Collins J, Abumrad NN. Role of leucine and other amino acids in regulating protein metabolism in vivo. Am J Physiol. 1992 Jun;262(6 Pt 1):E925-35.
12. Svanberg E, Moller-Loswick AC, Matthews DE, Korner U, Andersson M, Lundholm K. Effects of amino acids on synthesis and degradation of skeletal muscle proteins in humans. Am J Physiol. 1996 Oct;271(4 Pt 1):E718-24.
13. Gravholt CH, Moller N, Jensen MD, Christiansen JS, Schmitz O. Physiological levels of glucagon do not influence lipolysis in abdominal adipose tissue as assessed by microdialysis. J Clin Endocrinol Metab. 2001 May;86(5):2085-9.
14. Charlton MR, Adey DB, Nair KS. Evidence for a catabolic role of glucagon during an amino acid load. J Clin Invest. 1996 Jul 1;98(1):90-9.
15. Liljenquist JE, Bomboy JD, Lewis SB, et al. 1974 Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men. J Clin Invest. 53:190?197.
16. Gerich JE, Lorenzi M, Bier DM, et al. 1976 Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. J Clin Invest. 57:875?884.
17. Schneider SH, Fineberg SE, Blackburn GL. 1981 The acute metabolic effects of glucagon and its interactions with insulin in forearm tissue. Diabetologia. 20:616?624.
18. Carlson MG, Snead WL, Campbell PJ. 1993 Regulation of free fatty acid metabolism by glucagon. J Clin Endocrinol Metab. 77:11?15.
19. Jensen MD, Heiling VJ, Miles JM. 1991 Effects of glucagon on free fatty acid metabolism in humans. J Clin Endocrinol Metab. 72:308?315.
20. Liu D, Moberg E, Kollind M, Lins PE, Adamson U. A high concentration of circulating insulin suppresses the glucagon response to hypoglycemia in normal man. J Clin Endocrinol Metab. 1991 Nov;73(5):1123-8.
21. Moller N, Jorgensen JO, Abildgard N, Orskov L, Schmitz O, Christiansen JS.
22. Jorgensen JOL, Møller J, Alberti KG, et al. Marked effects of sustained low growth hormone (GH) levels on day-to-day fuel metabolism: studies in GH-deficient patients and healthy untreated subjects. J Clin Endocrinol Metab. 1993;77:1589?1596.
23. Moller N, Schmitz O, Pørksen N, Møller J, Jørgensen JOL. Dose-response studies on the metabolic effects of a growth hormone pulse in humans. Metabolism. 1992;41:172?175.
24. Fowelin J, Attvall S, von Schenck H, Smith U, Lager I. Characterization of the insulin-antagonistic effect of growth hormone in man. Diabetologia. 1991;34:500?506.
25. Moller N, Norrelund H. The role of growth hormone in the regulation of protein metabolism with particular reference to conditions of fasting. Horm Res. 2003;59 Suppl 1:62-8.
26. Clemmons DR, Snyder DK, Williams R, Underwood LE: Growth hormone administration conserves lean body mass during dietary restriction in obese subjects. J Clin Endocrinol Metab 1987;64:878-883.
27. Gamrin L, Essen P, Hultman E, McNurlan MA, Garlick PJ, Wernerman J. Protein-sparing effect in skeletal muscle of growth hormone treatment in critically ill patients. Ann Surg. 2000 Apr;231(4):577-86.
28. Lundeberg S, Belfrage M, Wernerman J, von der Decken A, Thunell S, Vinnars E: Growth hormone improves muscle protein metabolism and whole body nitrogen economy in man during a hyponitrogenous diet. Metabolism 1991;40:315-322.
29. Carli F, Webster JD, Halliday D: Growth hormone modulates amino acid oxidation in the surgical patient: leucine kinetics during the fasted and fed state using moderate nitrogenous and caloric diet and recombinant human growth hormone. Metabolism 1997;46:23-28.
30. Copeland KC, Nair KS: Acute growth hormone effects on amino acid and lipid metabolism. J Clin Endocrinol Metab 1994;78:1040-1047.
31. Fryburg DA, Barrett EJ: Growth hormone acutely stimulates skeletal muscle but not whole-body protein synthesis in humans. Metabolism 1993;42:1223-1227.
32. Divertie GD, Jensen MD, Miles JM. Stimulation of lipolysis in humans by physiological hypercortisolemia. Diabetes. 1991 Oct;40(10):1228-32.
33. Powers, SK, Howley, ET. Exercise physiology, 4th edition. Boston: McGraw Hill, 2001.
34. Brillon DJ, Zheng B, Campbell RG, Matthews DE. Effect of cortisol on energy expenditure and amino acid metabolism in humans. Am J Physiol. 1995 Mar;268(3 Pt 1):E501-13.
35. Simmons PS, Miles JM, Gerich JE, Haymond MW. Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range. J Clin Invest. 1984 Feb;73(2):412-20.
36. Rizza RA, Mandarino LJ, Gerich JE. Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor detect of insulin action. J Clin Endocrinol Metab. 1982 Jan;54(1):131-8.
37. Sherwin RS, Sacca L. Effect of epinephrine on glucose metabolism in humans: contribution of the liver. Am J Physiol. 1984 Aug;247(2 Pt 1):E157-65.
38. Sacca L, Vigorito C, Cicala M, Corso G, Sherwin RS. Role of gluconeogenesis in epinephrine-stimulated hepatic glucose production in humans. Am J Physiol. 1983 Sep;245(3):E294-302.
39. Cryer PE. Adrenaline: a physiological metabolic regulatory hormone in humans? Int J Obes Relat Metab Disord. 1993 Dec;17 Suppl 3:S43-6; discussion S68.
40. Rizza R, Haymond M, Cryer P, Gerich J. Differential effects of epinephrine on glucose production and disposal in man. Am J Physiol. 1979 Oct;237(4):E356-62.
41. Fryburg DA, Gelfand RA, Jahn LA, Oliveras D, Sherwin RS, Sacca L, Barrett EJ. Effects of epinephrine on human muscle glucose and protein metabolism. Am J Physiol. 1995 Jan;268(1 Pt 1):E55-9.
42. Miles JM, Nissen SL, Gerich JE, Haymond MW. Effects of epinephrine infusion on leucine and alanine kinetics in humans. Am J Physiol. 1984 Aug;247(2 Pt 1):E166-72.
43. Kraenzlin ME, Keller U, Keller A, Thelin A, Arnaud MJ, Stauffacher W.
44. Galbo H, Holst JJ, Christensen NJ. Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. J Appl Physiol. 1975 Jan;38(1):70-6.
45. Miller SL, Maresh CM, Armstrong LE, Ebbeling CB, Lennon S, Rodriguez NR.
46. Bonen A, Belcastro AN, MacIntyre K, Gardner J. Hormonal responses during intense exercise preceded by glucose ingestion. Can J Appl Sport Sci. 1980 Jun;5(2):85-90.
47. Tatar P, Kozlowski S, Vigas M, Nazar K, Kvetnansky R, Jezova D, Kaciuba-Uscilko H. Endocrine response to physical efforts with equivalent total work loads but different intensities in man. Endocrinol Exp. 1984 Dec;18(4):233-9.
48. Kjaer M. Hepatic glucose production during exercise. Adv Exp Med Biol. 1998;441:117-27.
49. Sutton J, Lazarus L. Growth hormone in exercise: comparison of physiological and pharmacological stimuli. J Appl Physiol. 1976 Oct;41(4):523-7.
50. Wideman L, Weltman JY, Hartman ML, Veldhuis JD, Weltman A. Growth hormone release during acute and chronic aerobic and resistance exercise: recent findings. Sports Med. 2002;32(15):987-1004.
51. Bunt JC, Boileau RA, Bahr JM, Nelson RA. Sex and training differences in human growth hormone levels during prolonged exercise. J Appl Physiol. 1986 Nov;61(5):1796-801.
52. Baechle, TR, Earle, RW. Essentials of Strength and Conditioning, 2nd edition. Champaign, IL: Human Kinetics, 2001.
53. Bonen A. Effects of exercise on excretion rates of urinary free cortisol. J Appl Physiol. 1976 Feb;40(2):155-8.
54. Rasmuson S, Olsson T, Hagg E. A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis. Clin Endocrinol (Oxf). 1996 Feb;44(2):151-6.
55. Galbo H, Holst JJ, Christensen NJ. Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. J Appl Physiol. 1975 Jan;38(1):70-6.
56. de Diego Acosta AM, Garcia JC, Fernandez-Pastor VJ, Peran S, Ruiz M, Guirado F. Influence of fitness on the integrated neuroendocrine response to aerobic exercise until exhaustion. J Physiol Biochem. 2001 Dec;57(4):313-20.
57. Kraemer WJ, Dziados JE, Gordon SE, Marchitelli LJ, Fry AC, Reynolds KL.
58. McMurray RG, Forsythe WA, Mar MH, Hardy CJ. Exercise intensity-related responses of beta-endorphin and catecholamines. Med Sci Sports Exerc. 1987 Dec;19(6):570-4.
59. Kraemer WJ, Noble B, Culver B, Lewis RV. Changes in plasma proenkephalin peptide F and catecholamine levels during graded exercise in men. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6349-51.
60. Sothmann MS, Blaney J, Woulfe T, Donahue-Fuhrman S, Lefever K, Gustafson AB, Murthy VS. Plasma free and sulfoconjugated catecholamines during sustained exercise. J Appl Physiol. 1990 Feb;68(2):452-6.
61. Rostrup M, Westheim A, Refsum HE, Holme I, Eide I. Arterial and venous plasma catecholamines during submaximal steady-state exercise. Clin Physiol. 1998 Mar;18(2):109-15.
62. Sahlin K. Muscle glucose metabolism during exercise. Ann Med. 1990 Jun;22(3):85-9.
63. Coggan AR, Coyle EF. Carbohydrate ingestion during prolonged exercise: effects on metabolism and performance. Exerc Sport Sci Rev. 1991;19:1-40.
64. Ivy JL. The insulin-like effect of muscle contraction. Exerc Sport Sci Rev. 1987;15:29-51.
65. Wojtaszewski JF, Richter EA. Glucose utilization during exercise: influence of endurance training. Acta Physiol Scand. 1998 Mar;162(3):351-8.
66. Richter EA, Kristiansen S, Wojtaszewski J, Daugaard JR, Asp S, Hespel P, Kiens B. Training effects on muscle glucose transport during exercise. Adv Exp Med Biol. 1998;441:107-16.
67. Goodyear LJ, Kahn BB. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med. 1998;49:235-61.
68. Ivy JL. Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med. 1997 Nov;24(5):321-36.
69. Ivy JL, Kuo CH. Regulation of GLUT4 protein and glycogen synthase during muscle glycogen synthesis after exercise. Acta Physiol Scand. 1998 Mar;162(3):295-304.
70. Kennedy JW, Hirshman MF, Gervino EV, Ocel JV, Forse RA, Hoenig SJ, Aronson D, Goodyear LJ, Horton ES. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes. 1999 May;48(5):1192-7.
71. Douen AG, Ramlal T, Rastogi S, Bilan PJ, Cartee GD, Vranic M, Holloszy JO, Klip A. Exercise induces recruitment of the “insulin-responsive glucose transporter”. Evidence for distinct intracellular insulin- and exercise-recruitable transporter pools in skeletal muscle. J Biol Chem. 1990 Aug 15;265(23):13427-30.
72. Fushiki T, Wells JA, Tapscott EB, Dohm GL. Changes in glucose transporters in muscle in response to exercise. Am J Physiol. 1989 May;256(5 Pt 1):E580-7.
73. Hayashi T, Wojtaszewski JF, Goodyear LJ. Exercise regulation of glucose transport in skeletal muscle. Am J Physiol. 1997 Dec;273(6 Pt 1):E1039-51.
74. Yeh JI, Gulve EA, Rameh L, Birnbaum MJ. The effects of wortmannin on rat skeletal muscle. Dissociation of signaling pathways for insulin- and contraction-activated hexose transport. J Biol Chem. 1995 Feb 3;270(5):2107-11.
75. Brozinick JT Jr, Etgen GJ Jr, Yaspelkis BB 3rd, Ivy JL. Contraction-activated glucose uptake is normal in insulin-resistant muscle of the obese Zucker rat. J Appl Physiol. 1992 Jul;73(1):382-7.
76. Henriksen EJ, Bourey RE, Rodnick KJ, Koranyi L, Permutt MA, Holloszy JO.
77. Phillips, S., et al. Increments in skeletal muscle GLUT-1 and GLUT-4 after endurance training in humans. Am J Physiol. 1996 Mar;270(3 Pt 1):E456-62.
78. Johannsson, E., Effect of cross-reinnervation on the expression of GLUT-4 and GLUT-1 in slow and fast rat muscles. Am J Physiol. 1996 Jun;270(6 Pt 2):R1355-60.
79. Holloszy JO, Kohrt WM, Hansen PA. The regulation of carbohydrate and fat metabolism during and after exercise. Front Biosci. 1998 Sep 15;3:D1011-27.
80. Jensen MD. Fate of fatty acids at rest and during exercise: regulatory mechanisms. Acta Physiol Scand. 2003 Aug;178(4):385-90.
81. Spriet LL, Watt MJ. Regulatory mechanisms in the interaction between carbohydrate and lipid oxidation during exercise. Acta Physiol Scand. 2003 Aug;178(4):443-52.
82.Coggan AR. Plasma glucose metabolism during exercise in humans. Sports Med. 1991 Feb;11(2):102-24.