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. 1984 Mar;73(3):633–639. doi: 10.1172/JCI111253

Effect of beta and alpha adrenergic blockade on glucose-induced thermogenesis in man.

R A DeFronzo, D Thorin, J P Felber, D C Simonson, D Thiebaud, E Jequier, A Golay
PMCID: PMC425062  PMID: 6368584

Abstract

After intravenous glucose/insulin infusion there is an increase in oxygen consumption and energy expenditure that has been referred to as thermogenesis. To examine the contribution of the beta and alpha adrenergic nervous system to this thermogenic response, 12 healthy volunteers participated in three studies: (a) euglycemic insulin (plasma insulin approximately 100 microunits/ml) clamp study (n = 12); (b) insulin clamp study after beta adrenergic blockade with intravenous propranolol for 1 h (n = 12); (c) insulin clamp study after alpha adrenergic blockade with phentolamine for 1 h (n = 5). During the control insulin clamp study total glucose uptake, glucose oxidation and nonoxidative glucose uptake averaged 7.85 +/- 0.47, 2.62 +/- 0.22, and 5.23 +/- 0.51 mg/kg X min. After propranolol infusion, insulin-mediated glucose uptake was significantly reduced, 6.89 +/- 0.41 (P less than 0.02). This decrease was primarily the result of a decrease in glucose oxidation (1.97 +/- 0.19 mg/kg X min, P less than 0.01) without any change in nonoxidative glucose metabolism. Phentolamine administration had no effect on total glucose uptake, glucose oxidation, or nonoxidative glucose disposal. The increments in energy expenditure (0.10 +/- 0.01 vs. 0.03 +/- 0.01 kcal/min) and glucose/insulin-induced thermogenesis (4.9 +/- 0.5 vs. 1.5 +/- 0.5%) were reduced by 70% during the propranolol/insulin clamp study. The increments in energy expenditure (0.12 +/- 0.03 kcal/min) and thermogenesis (5.0 +/- 1.5%) were not affected by phentolamine. These results indicate that activation of the beta adrenergic receptor plays an important role in the insulin/glucose-mediated increase in energy expenditure and thermogenesis. In contrast, the alpha adrenergic receptor does not appear to participate in this response.

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Selected References

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  1. Acheson K., Jéquier E., Wahren J. Influence of beta-adrenergic blockade on glucose-induced thermogenesis in man. J Clin Invest. 1983 Sep;72(3):981–986. doi: 10.1172/JCI111070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BALL E. G., JUNGAS R. L. SOME EFFECTS OF HORMONES ON THE METABOLISM OF ADIPOSE TISSUE. Recent Prog Horm Res. 1964;20:183–214. [PubMed] [Google Scholar]
  3. Ball E. G. Some energy relationships in adipose tissue. Ann N Y Acad Sci. 1965 Oct 8;131(1):225–234. doi: 10.1111/j.1749-6632.1965.tb34791.x. [DOI] [PubMed] [Google Scholar]
  4. Bergström J., Hultman E. Synthesis of muscle glycogen in man after glucose and fructose infusion. Acta Med Scand. 1967 Jul;182(1):93–107. doi: 10.1111/j.0954-6820.1967.tb11503.x. [DOI] [PubMed] [Google Scholar]
  5. 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. doi: 10.1111/j.1365-2362.1971.tb00559.x. [DOI] [PubMed] [Google Scholar]
  6. Björntorp P., Krotkiewski M., Larsson B., Somlo-Szücs Z. Effects of feeding states on lipid radioactivity in liver, muscle and adipose tissue after injection of labelled glucose in the rat. Acta Physiol Scand. 1970 Sep;80(1):29–38. doi: 10.1111/j.1748-1716.1970.tb04766.x. [DOI] [PubMed] [Google Scholar]
  7. Björntorp P., Sjöström L. Carbohydrate storage in man: speculations and some quantitative considerations. Metabolism. 1978 Dec;27(12 Suppl 2):1853–1865. doi: 10.1016/s0026-0495(78)80004-3. [DOI] [PubMed] [Google Scholar]
  8. Bursztein S., Saphar P., Glaser P., Taitelman U., de Myttenaere S., Nedey R. Determination of energy metabolism from respiratory functions alone. J Appl Physiol Respir Environ Exerc Physiol. 1977 Jan;42(1):117–119. doi: 10.1152/jappl.1977.42.1.117. [DOI] [PubMed] [Google Scholar]
  9. Chiasson J. L., Dietz M. R., Shikama H., Wootten M., Exton J. H. Insulin regulation of skeletal muscle glycogen metabolism. Am J Physiol. 1980 Jul;239(1):E69–E74. doi: 10.1152/ajpendo.1980.239.1.E69. [DOI] [PubMed] [Google Scholar]
  10. Clausen T., Kohn P. G. The effect of insulin on the transport of sodium and potassium in rat soleus muscle. J Physiol. 1977 Feb;265(1):19–42. doi: 10.1113/jphysiol.1977.sp011703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cryer P. E. Isotope-derivative measurements of plasma norepinephrine and epinephrine in man. Diabetes. 1976 Nov;25(11):1071–1082. doi: 10.2337/diab.25.11.1071. [DOI] [PubMed] [Google Scholar]
  12. DeFronzo R. A., Ferrannini E., Hendler R., Felig P., Wahren J. Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia in man. Diabetes. 1983 Jan;32(1):35–45. doi: 10.2337/diab.32.1.35. [DOI] [PubMed] [Google Scholar]
  13. DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Garrow J. S., Hawes S. F. The role of amino acid oxidation in causing specific dynamic action' in man. Br J Nutr. 1972 Jan;27(1):211–219. doi: 10.1079/bjn19720084. [DOI] [PubMed] [Google Scholar]
  16. Hers H. G. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. doi: 10.1146/annurev.bi.45.070176.001123. [DOI] [PubMed] [Google Scholar]
  17. Hultman E., Bergström J. Muscle glycogen synthesis in relation to diet studied in normal subjects. Acta Med Scand. 1967 Jul;182(1):109–117. doi: 10.1111/j.0954-6820.1967.tb11504.x. [DOI] [PubMed] [Google Scholar]
  18. Jeffcoate S. L., Moody A. J. The role of the liver in the disposal of orally administered 14C-glucose in the normal rat. Diabetologia. 1969 Oct;5(5):293–299. doi: 10.1007/BF00452901. [DOI] [PubMed] [Google Scholar]
  19. Jung R. T., Shetty P. S., James W. P., Barrand M. A., Callingham B. A. Reduced thermogenesis in obesity. Nature. 1979 May 24;279(5711):322–323. doi: 10.1038/279322a0. [DOI] [PubMed] [Google Scholar]
  20. Kusaka M., Ui M. Activation of the Cori cycle by epinephrine. Am J Physiol. 1977 Feb;232(2):E145–E155. doi: 10.1152/ajpendo.1977.232.2.E145. [DOI] [PubMed] [Google Scholar]
  21. Landsberg L., Young J. B. Fasting, feeding and regulation of the sympathetic nervous system. N Engl J Med. 1978 Jun 8;298(23):1295–1301. doi: 10.1056/NEJM197806082982306. [DOI] [PubMed] [Google Scholar]
  22. McGuire E. A., Helderman J. H., Tobin J. D., Andres R., Berman M. Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol. 1976 Oct;41(4):565–573. doi: 10.1152/jappl.1976.41.4.565. [DOI] [PubMed] [Google Scholar]
  23. Müller-Hess R., Geser C. A., Pittet P., Chappuis P., Jéquier E., Felber J. P. Interactions of insulin and epinephrine in human metabolism: their influence on carbohydrate and lipid oxidation rate. Diabete Metab. 1975 Sep;1(3):151–157. [PubMed] [Google Scholar]
  24. Nilsson L. H., Hultman E. Liver and muscle glycogen in man after glucose and fructose infusion. Scand J Clin Lab Invest. 1974 Feb;33(1):5–10. doi: 10.3109/00365517409114190. [DOI] [PubMed] [Google Scholar]
  25. Perkins M. N., Rothwell N. J., Stock M. J., Stone T. W. Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature. 1981 Jan 29;289(5796):401–402. doi: 10.1038/289401a0. [DOI] [PubMed] [Google Scholar]
  26. Perkins M. N., Rothwell N. J., Stock M. J., Stone T. W. Activation of brown adipose tissue thermogenesis by the ventromedial hypothalamus. Nature. 1981 Jan 29;289(5796):401–402. doi: 10.1038/289401a0. [DOI] [PubMed] [Google Scholar]
  27. Pittet P., Chappuis P., Acheson K., De Techtermann F., Jéquier E. Thermic effect of glucose in obese subjects studied by direct and indirect calorimetry. Br J Nutr. 1976 Mar;35(2):281–292. doi: 10.1079/bjn19760033. [DOI] [PubMed] [Google Scholar]
  28. Pittet P., Gygax P. H., Jéquier E. Thermic effect of glucose and amino acids in man studied by direct and indirect calorimetry. Br J Nutr. 1974 May;31(3):343–349. doi: 10.1079/bjn19740042. [DOI] [PubMed] [Google Scholar]
  29. Radziuk J. Sources of carbon in hepatic glycogen synthesis during absorption of an oral glucose load in humans. Fed Proc. 1982 Jan;41(1):110–116. [PubMed] [Google Scholar]
  30. Roch-Norlund A. E., Bergström J., Hultman E. Muscle glycogen and glycogen synthetase in normal subjects and in patients with diabetes mellitus. Effect of intravenous glucose and insulin administration. Scand J Clin Lab Invest. 1972 Sep;30(1):77–84. doi: 10.3109/00365517209081094. [DOI] [PubMed] [Google Scholar]
  31. Rothwell N. J., Stock M. J. A role for brown adipose tissue in diet-induced thermogenesis. Nature. 1979 Sep 6;281(5726):31–35. doi: 10.1038/281031a0. [DOI] [PubMed] [Google Scholar]
  32. Rothwell N. J., Stock M. J. A role for insulin in the diet-induced thermogenesis of cafeteria-fed rats. Metabolism. 1981 Jul;30(7):673–678. doi: 10.1016/0026-0495(81)90082-2. [DOI] [PubMed] [Google Scholar]
  33. Rothwell N. J., Stock M. J., Tyzbir R. S. Mechanisms of thermogenesis induced by low protein diets. Metabolism. 1983 Mar;32(3):257–261. doi: 10.1016/0026-0495(83)90190-7. [DOI] [PubMed] [Google Scholar]
  34. Rowe J. W., Young J. B., Minaker K. L., Stevens A. L., Pallotta J., Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes. 1981 Mar;30(3):219–225. doi: 10.2337/diab.30.3.219. [DOI] [PubMed] [Google Scholar]
  35. SWIFT R. W., BARRON G. P., FISHER K. H., FRENCH C. E., HARTSOOK E. W., HERSHBERGER T. V., KECK E., LONG T. A., MAGRUDER N. D. The effect of high versus low protein equicaloric diets on the heat production of human subjects. J Nutr. 1958 May 10;65(1):89–102. doi: 10.1093/jn/65.1.89. [DOI] [PubMed] [Google Scholar]
  36. Schwartz R. S., Halter J. B., Bierman E. L. Reduced thermic effect of feeding in obesity: role of norepinephrine. Metabolism. 1983 Feb;32(2):114–117. doi: 10.1016/0026-0495(83)90214-7. [DOI] [PubMed] [Google Scholar]
  37. Shikama H., Ui M. Glucose load diverts hepatic gluconeogenic product from glucose to glycogen in vivo. Am J Physiol. 1978 Oct;235(4):E354–E360. doi: 10.1152/ajpendo.1978.235.4.E354. [DOI] [PubMed] [Google Scholar]
  38. Swindells Y. E. The influence of activity and size of meals on caloric response in women. Br J Nutr. 1972 Jan;27(1):65–73. doi: 10.1079/bjn19720070. [DOI] [PubMed] [Google Scholar]
  39. Thiebaud D., Acheson K., Schutz Y., Felber J. P., Golay A., Defronzo R. A., Jéquier E. Stimulation of thermogenesis in men after combined glucose-long-chain triglyceride infusion. Am J Clin Nutr. 1983 Apr;37(4):603–611. doi: 10.1093/ajcn/37.4.603. [DOI] [PubMed] [Google Scholar]
  40. Thiebaud D., Jacot E., DeFronzo R. A., Maeder E., Jequier E., Felber J. P. The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man. Diabetes. 1982 Nov;31(11):957–963. doi: 10.2337/diacare.31.11.957. [DOI] [PubMed] [Google Scholar]
  41. Thiebaud D., Schutz Y., Acheson K., Jacot E., DeFronzo R. A., Felber J. P., Jequier E. Energy cost of glucose storage in human subjects during glucose-insulin infusions. Am J Physiol. 1983 Mar;244(3):E216–E221. doi: 10.1152/ajpendo.1983.244.3.E216. [DOI] [PubMed] [Google Scholar]
  42. Welle S. L., Campbell R. G. Normal thermic effect of glucose in obese women. Am J Clin Nutr. 1983 Jan;37(1):87–92. doi: 10.1093/ajcn/37.1.87. [DOI] [PubMed] [Google Scholar]
  43. Welle S., Lilavivat U., Campbell R. G. Thermic effect of feeding in man: increased plasma norepinephrine levels following glucose but not protein or fat consumption. Metabolism. 1981 Oct;30(10):953–958. doi: 10.1016/0026-0495(81)90092-5. [DOI] [PubMed] [Google Scholar]
  44. Young J. B., Landsberg L. Effect of diet and cold exposure on norepinephrine turnover in pancreas and liver. Am J Physiol. 1979 May;236(5):E524–E533. doi: 10.1152/ajpendo.1979.236.5.E524. [DOI] [PubMed] [Google Scholar]
  45. Young J. B., Landsberg L. Stimulation of the sympathetic nervous system during sucrose feeding. Nature. 1977 Oct 13;269(5629):615–617. doi: 10.1038/269615a0. [DOI] [PubMed] [Google Scholar]
  46. Young J. B., Rowe J. W., Pallotta J. A., Sparrow D., Landsberg L. Enhanced plasma norepinephrine response to upright posture and oral glucose administration in elderly human subjects. Metabolism. 1980 Jun;29(6):532–539. doi: 10.1016/0026-0495(80)90078-5. [DOI] [PubMed] [Google Scholar]
  47. Zwillich C., Martin B., Hofeldt F., Charles A., Subryan V., Burman K. Lack of effects of beta sympathetic blockade on the metabolic and respiratory responses to carbohydrate feeding. Metabolism. 1981 May;30(5):451–456. doi: 10.1016/0026-0495(81)90179-7. [DOI] [PubMed] [Google Scholar]

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