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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jun;73(6):1648–1658. doi: 10.1172/JCI111371

Adrenergic blockade alters glucose kinetics during exercise in insulin-dependent diabetics.

D C Simonson, V Koivisto, R S Sherwin, E Ferrannini, R Hendler, A Juhlin-Dannfelt, R A DeFronzo
PMCID: PMC437075  PMID: 6327767

Abstract

We investigated the effects of alpha and/or beta adrenergic blockade (with phentolamine and/or propranolol) on glucose homeostasis during exercise in six normal subjects and in seven Type I diabetic subjects. The diabetics received a low dose insulin infusion (0.07 mU/kg X min) designed to maintain plasma glucose at approximately 150 mg/dl. In normals, neither alpha, beta, nor combined alpha and beta adrenergic blockade altered glucose production, glucose uptake, or plasma glucose concentration during exercise. In diabetics, exercise alone produced a decline in glucose concentration from 144 to 116 mg/dl. This was due to a slightly diminished rise in hepatic glucose production in association with a normal increase in glucose uptake. When exercise was performed during beta adrenergic blockade, the decline in plasma glucose was accentuated. An exogenous glucose infusion (2.58 mg/kg X min) was required to prevent glucose levels from falling below 90 mg/dl. The effect of beta blockade was accounted for by a blunted rise in hepatic glucose production and an augmented rise in glucose utilization. These alterations were unrelated to changes in plasma insulin and glucagon levels, which were similar in the presence and absence of propranolol. In contrast, when the diabetics exercised during alpha adrenergic blockade, plasma glucose concentration rose from 150 to 164 mg/dl. This was due to a significant increase in hepatic glucose production and a small decline in exercise-induced glucose utilization. These alterations also could not be explained by differences in insulin and glucagon levels. We conclude that the glucose homeostatic response to exercise in insulin-dependent diabetics, in contrast to healthy controls, is critically dependent on the adrenergic nervous system.

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Selected References

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  1. Aguilar-Parada E., Eisentraut A. M., Unger R. H. Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci. 1969 Jun;257(6):415–419. doi: 10.1097/00000441-196906000-00008. [DOI] [PubMed] [Google Scholar]
  2. 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. doi: 10.1172/JCI107645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allison S. P., Chamberlain M. J., Miller J. E., Ferguson R., Gillett A. P., Bemand B. V., Saunders R. A. Effects of propranolol on blood sugar, insulin and free fatty acids. Diabetologia. 1969 Oct;5(5):339–342. doi: 10.1007/BF00452909. [DOI] [PubMed] [Google Scholar]
  4. Altszuler N., Barkai A., Bjerknes C., Gottlieb B., Steele R. Glucose turnover values in the dog obtained with various species of labeled glucose. Am J Physiol. 1975 Dec;229(6):1662–1667. doi: 10.1152/ajplegacy.1975.229.6.1662. [DOI] [PubMed] [Google Scholar]
  5. Christensen N. J., Galbo H., Hansen J. F., Hesse B., Richter E. A., Trap-Jensen J. Catecholamines and exercise. Diabetes. 1979 Jan;28 (Suppl 1):58–62. doi: 10.2337/diab.28.1.s58. [DOI] [PubMed] [Google Scholar]
  6. DOLE V. P. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150–154. doi: 10.1172/JCI103259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Day J. L. The metabolic consequences of adrenergic blockade: a reveiw. Metabolism. 1975 Aug;24(8):987–996. doi: 10.1016/0026-0495(75)90090-6. [DOI] [PubMed] [Google Scholar]
  8. DeFronzo R. A., Hendler R., Simonson D. Insulin resistance is a prominent feature of insulin-dependent diabetes. Diabetes. 1982 Sep;31(9):795–801. doi: 10.2337/diab.31.9.795. [DOI] [PubMed] [Google Scholar]
  9. Deibert D. C., DeFronzo R. A. Epinephrine-induced insulin resistance in man. J Clin Invest. 1980 Mar;65(3):717–721. doi: 10.1172/JCI109718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Felig P., Wahren J. Fuel homeostasis in exercise. N Engl J Med. 1975 Nov 20;293(21):1078–1084. doi: 10.1056/NEJM197511202932107. [DOI] [PubMed] [Google Scholar]
  11. Felig P., Wahren J. Role of insulin and glucagon in the regulation of hepatic glucose production during exercise. Diabetes. 1979 Jan;28 (Suppl 1):71–75. doi: 10.2337/diab.28.1.s71. [DOI] [PubMed] [Google Scholar]
  12. Galbo H., Christensen N. J., Holst J. J. Catecholamines and pancreatic hormones during autonomic blockade in exercising man. Acta Physiol Scand. 1977 Dec;101(4):428–437. doi: 10.1111/j.1748-1716.1977.tb06026.x. [DOI] [PubMed] [Google Scholar]
  13. Galbo H., Christensen N. J., Mikines K. J., Sonne B., Hilsted J., Hagen C., Fahrenkrug J. The effect of fasting on the hormonal response to graded exercise. J Clin Endocrinol Metab. 1981 Jun;52(6):1106–1112. doi: 10.1210/jcem-52-6-1106. [DOI] [PubMed] [Google Scholar]
  14. Galbo H., Holst J. J., Christensen N. J., Hilsted J. Glucagon and plasma catecholamines during beta-receptor blockade in exercising man. J Appl Physiol. 1976 Jun;40(6):855–863. doi: 10.1152/jappl.1976.40.6.855. [DOI] [PubMed] [Google Scholar]
  15. Galbo H., Richter E. A., Hilsted J., Holst J. J., Christensen N. J., Henriksson J. Hormonal regulation during prolonged exercise. Ann N Y Acad Sci. 1977;301:72–80. doi: 10.1111/j.1749-6632.1977.tb38187.x. [DOI] [PubMed] [Google Scholar]
  16. Hartley L. H., Mason J. W., Hogan R. P., Jones L. G., Kotchen T. A., Mougey E. H., Wherry F. E., Pennington L. L., Ricketts P. T. Multiple hormonal responses to graded exercise in relation to physical training. J Appl Physiol. 1972 Nov;33(5):602–606. doi: 10.1152/jappl.1972.33.5.602. [DOI] [PubMed] [Google Scholar]
  17. Harvey W. D., Faloona G. R., Unger R. H. The effect of adrenergic blockade on exercise-induced hyperglucagonemia. Endocrinology. 1974 May;94(5):1254–1258. doi: 10.1210/endo-94-5-1254. [DOI] [PubMed] [Google Scholar]
  18. Issekutz B., Jr Energy mobilization in exercising dogs. Diabetes. 1979 Jan;28 (Suppl 1):39–44. doi: 10.2337/diab.28.1.s39. [DOI] [PubMed] [Google Scholar]
  19. Issekutz B., Jr The role of hypoinsulinemia in exercise metabolism. Diabetes. 1980 Aug;29(8):629–635. doi: 10.2337/diab.29.8.629. [DOI] [PubMed] [Google Scholar]
  20. Kotler M. N., Berman L., Rubenstein A. H. Hypoglycaemia precipitated by propranolol. Lancet. 1966 Dec 24;2(7478):1389–1390. doi: 10.1016/s0140-6736(66)90423-5. [DOI] [PubMed] [Google Scholar]
  21. Kuzuya H., Blix P. M., Horwitz D. L., Steiner D. F., Rubenstein A. H. Determination of free and total insulin and C-peptide in insulin-treated diabetics. Diabetes. 1977 Jan;26(1):22–29. doi: 10.2337/diab.26.1.22. [DOI] [PubMed] [Google Scholar]
  22. Lager I., Blohmé G., Smith U. Effect of cardioselective and non-selective beta-blockade on the hypoglycaemic response in insulin-dependent diabetics. Lancet. 1979 Mar 3;1(8114):458–462. doi: 10.1016/s0140-6736(79)90821-3. [DOI] [PubMed] [Google Scholar]
  23. Luyckx A. S., Lefebvre P. J. Mechanisms involved in the exercise-induced increase in glucagon secretion in rats. Diabetes. 1974 Feb;23(2):81–93. doi: 10.2337/diab.23.2.81. [DOI] [PubMed] [Google Scholar]
  24. Muller W. A., Girardier L., Seydoux J., Berger M., Renold A. E., Vranic M. Extrapancreatic glucagon and glucagonlike immunoreactivity in depancreatized dogs. A quantitative assessment of secretion rates and anatomical delineation of sources. J Clin Invest. 1978 Jul;62(1):124–132. doi: 10.1172/JCI109096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. NOVAK M. COLORIMETRIC ULTRAMICRO METHOD FOR THE DETERMINATION OF FREE FATTY ACIDS. J Lipid Res. 1965 Jul;6:431–433. [PubMed] [Google Scholar]
  26. Richter E. A., Ruderman N. B., Galbo H. Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle. Acta Physiol Scand. 1982 Nov;116(3):215–222. doi: 10.1111/j.1748-1716.1982.tb07133.x. [DOI] [PubMed] [Google Scholar]
  27. Rizza R. A., Cryer P. E., Haymond M. W., Gerich J. E. Adrenergic mechanisms for the effects of epinephrine on glucose production and clearance in man. J Clin Invest. 1980 Mar;65(3):682–689. doi: 10.1172/JCI109714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Robertson R. P., Porte D., Jr Adrenergic modulation of basal insulin secretion in man. Diabetes. 1973 Jan;22(1):1–8. doi: 10.2337/diab.22.1.1. [DOI] [PubMed] [Google Scholar]
  29. Rosselin G., Assan R., Yalow R. S., Berson S. A. Separation of antibody-bound and unbound peptide hormones labelled with iodine-131 by talcum powder and precipitated silica. Nature. 1966 Oct 22;212(5060):355–357. doi: 10.1038/212355a0. [DOI] [PubMed] [Google Scholar]
  30. STEELE R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci. 1959 Sep 25;82:420–430. doi: 10.1111/j.1749-6632.1959.tb44923.x. [DOI] [PubMed] [Google Scholar]
  31. Saccà L., Vigorito C., Cicala M., Ungaro B., Sherwin R. S. Mechanisms of epinephrine-induced glucose intolerance in normal humans. J Clin Invest. 1982 Feb;69(2):284–293. doi: 10.1172/JCI110451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shamoon H., Hendler R., Sherwin R. S. Altered responsiveness to cortisol, epinephrine, and glucagon in insulin-infused juvenile-onset diabetics. A mechanism for diabetic instability. Diabetes. 1980 Apr;29(4):284–291. doi: 10.2337/diab.29.4.284. [DOI] [PubMed] [Google Scholar]
  33. Sherwin R. S., Shamoon H., Hendler R., Saccà L., Eigler N., Walesky M. Epinephrine and the regulation of glucose metabolism: effect of diabetes and hormonal interactions. Metabolism. 1980 Nov;29(11 Suppl 1):1146–1154. doi: 10.1016/0026-0495(80)90024-4. [DOI] [PubMed] [Google Scholar]
  34. Uusitupa M., Aro A., Pietikäinen M. Severe hypoglycaemia caused by physical strain and pindolol therapy. A case report. Ann Clin Res. 1980 Feb;12(1):25–27. [PubMed] [Google Scholar]
  35. Wahren J., Felig P., Ahlborg G., Jorfeldt L. Glucose metabolism during leg exercise in man. J Clin Invest. 1971 Dec;50(12):2715–2725. doi: 10.1172/JCI106772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zinman B., Vranic M., Albisser A. M., Leibel B. S., Marliss E. D. The role of insulin in the metabolic response to exercise in diabetic man. Diabetes. 1979 Jan;28 (Suppl 1):76–81. doi: 10.2337/diab.28.1.s76. [DOI] [PubMed] [Google Scholar]

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