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J Clin Invest. Dec 1981; 68(6): 1468–1474.
PMCID: PMC370949

Synergistic interaction between exercise and insulin on peripheral glucose uptake.


The interaction of exercise and insulin on glucose metabolism was examined in 10 healthy volunteers. Four study protocols were used: study 1: plasma insulin was raised by approximately 100 microunits/ml while plasma glucose was maintained at basal levels for 2 h (insulin clamp). Study 2: subjects performed 30 min of bicycle exercise at 40% of VO2 max. Study 3: an insulin clamp was performed as per study 1. Following 60 min of sustained hyperinsulinemia, however, subjects exercised for 30 min as per study 2. Study 4: subjects were studied as per study 3 except that catheters were inserted into the femoral artery and vein to quantitate leg glucose uptake. During the 60-90 min period of hyperinsulinemia (study 1), glucose uptake averaged 8.73 +/- 0.10 mg/kg per min. With exercise alone (study 2), the increment in peripheral glucose uptake was 1.43 +/- 0.30 mg/kg per min. When hyperinsulinemia and exercise were combined (study 3), glucose uptake averaged 15.06 +/- 0.98 mg/kg per min (P less than 0.01) and this was significantly (P less than 0.001) greater than the sum of glucose uptake when exercise and the insulin clamp were performed separately. The magnitude of rise in glucose uptake correlated closely with the increase in leg blood flow (r = 0.935, P less than 0.001), suggesting that the synergism is the result of increased blood flow and increased capillary surface area to exercising muscle. More than 85% of total body glucose metabolism during studies 1 and 3 was accounted for by skeletal muscle uptake. These results demonstrate that (a) insulin and exercise act synergistically to enhance glucose disposal in man, and (b) muscle is the primary tissue responsible for the increase in glucose metabolism following hyperinsulinemia and exercise.

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  • Berger M, Berchtold P, Cüppers HJ, Drost H, Kley HK, Müller WA, Wiegelmann W, Zimmerman-Telschow H, Gries FA, Krüskemper HL, et al. Metabolic and hormonal effects of muscular exercise in juvenile type diabetics. Diabetologia. 1977 Aug;13(4):355–365. [PubMed]
  • Wahren J, Felig P, Hagenfeldt L. Physical exercise and fuel homeostasis in diabetes mellitus. Diabetologia. 1978 Apr;14(4):213–222. [PubMed]
  • Berger M, Berchtold P. The role of physical exercise and training in the management of diabetes mellitus. Bibl Nutr Dieta. 1979;(27):41–54. [PubMed]
  • Wahren J, Felig P, Ahlborg G, Jorfeldt L. Glucose metabolism during leg exercise in man. J Clin Invest. 1971 Dec;50(12):2715–2725. [PMC free article] [PubMed]
  • Wahren J, Hagenfeldt L, Felig P. Splanchnic and leg exchange of glucose, amino acids, and free fatty acids during exercise in diabetes mellitus. J Clin Invest. 1975 Jun;55(6):1303–1314. [PMC free article] [PubMed]
  • Ahlborg G, Felig P, Hagenfeldt L, Hendler R, Wahren J. Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. J Clin Invest. 1974 Apr;53(4):1080–1090. [PMC free article] [PubMed]
  • Vranic M, Kawamori R, Pek S, Kovacevic N, Wrenshall GA. The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenuous exercise in dogs. J Clin Invest. 1976 Feb;57(2):245–255. [PMC free article] [PubMed]
  • Berger M, Hagg S, Ruderman NB. Glucose metabolism in perfused skeletal muscle. Interaction of insulin and exercise on glucose uptake. Biochem J. 1975 Jan;146(1):231–238. [PMC free article] [PubMed]
  • Pruett ED, Oseid S. Effect of exercise on glucose and insulin response to glucose infusion. Scand J Clin Lab Invest. 1970 Nov;26(3):277–285. [PubMed]
  • Maehlum S, Pruett ED. Muscular exercise and metabolism in male juvenile diabetics. II. Glucose tolerance after exercise. Scand J Clin Lab Invest. 1973 Oct;32(2):149–153. [PubMed]
  • Berger M, Halban PA, Muller WA, Offord RE, Renold AE, Vranic M. Mobilization of subcutaneously injected tritiated insulin in rats: effects of muscular exercise. Diabetologia. 1978 Aug;15(2):133–140. [PubMed]
  • Kawamori R, Vranic M. Mechanism of exercise-induced hypoglycemia in depancreatized dogs maintained on long-acting insulin. J Clin Invest. 1977 Feb;59(2):331–337. [PMC free article] [PubMed]
  • Koivisto VA, Felig P. Effects of leg exercise on insulin absorption in diabetic patients. N Engl J Med. 1978 Jan 12;298(2):79–83. [PubMed]
  • Murray FT, Zinman B, McClean PA, Denoga A, Albisser AM, Leibel BS, Nakhooda AF, Stokes EF, Marliss EB. The metabolic response to moderate exercise in diabetic man receiving intravenous and subcutaneous insulin. J Clin Endocrinol Metab. 1977 Apr;44(4):708–720. [PubMed]
  • Dandona P, Hooke D, Bell J. Exercise and insulin absorption from subcutaneous tissue. Br Med J. 1978 Feb 25;1(6111):479–480. [PMC free article] [PubMed]
  • Wahren J, Felig P, Hagenfeldt L. Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus. J Clin Invest. 1976 Apr;57(4):987–999. [PMC free article] [PubMed]
  • DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. [PubMed]
  • ASTRAND I. Aerobic work capacity in men and women with special reference to age. Acta Physiol Scand Suppl. 1960;49(169):1–92. [PubMed]
  • Wise JK, Hendler R, Felig P. Influence of glucocorticoids on glucagon secretion and plasma amino acid concentrations in man. J Clin Invest. 1973 Nov;52(11):2774–2782. [PMC free article] [PubMed]
  • Jorfeldt L, Wahren J. Leg blood flow during exercise in man. Clin Sci. 1971 Nov;41(5):459–473. [PubMed]
  • Wahren J, Jorfeldt L. Determination of leg blood flow during exercise in man: an indicator-dilution technique based on femoral venous dye infusion. Clin Sci Mol Med. 1973 Aug;45(2):135–146. [PubMed]
  • Bevegård BS, Shepherd JT. Regulation of the circulation during exercise in man. Physiol Rev. 1967 Apr;47(2):178–213. [PubMed]
  • Kalant N, Leibovici T, Rohan I, McNeil K. Effect of exercise on glucose and insulin utilization in the forearm. Metabolism. 1978 Mar;27(3):333–340. [PubMed]
  • Koivisto VA, Soman VR, Felig P. Effects of acute exercise on insulin binding to monocytes in obesity. Metabolism. 1980 Feb;29(2):168–172. [PubMed]
  • Björntorp P, Berchtold P, Holm J, Larsson B. The glucose uptake of human adipose tissue in obesity. Eur J Clin Invest. 1971 Sep;1(6):480–485. [PubMed]
  • Stolwijk JA, Hardy JD. Temperature regulation in man--a theoretical study. Pflugers Arch Gesamte Physiol Menschen Tiere. 1966;291(2):129–162. [PubMed]
  • Björntorp P, Sjöström L. Carbohydrate storage in man: speculations and some quantitative considerations. Metabolism. 1978 Dec;27(12 Suppl 2):1853–1865. [PubMed]
  • DeFronzo RA, Ferrannini E, Hendler R, Wahren J, Felig P. Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5173–5177. [PMC free article] [PubMed]

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