Summary
The magnitude and direction of the lipolytic and ketogenic responses following exogenous glucagon administration is controversial and consideration of the possible role of endogenous insulin secretion upon these events has not been clarified. The present study examines the role of endogenous insulin secretion in modulating the net lipolytic and ketogenic activity of glucagon. Three groups characterized by different levels of endogenous insulin secretory capacity were studied. In all three groups, the responses in plasma insulin, betahydroxybutyrate, and free fatty acids were observed following bolus administration of 1.0 μg/kg glucagon. In the obese subjects with increased endogenous insulin secretion, glucagon administration resulted in a decline below basal levels of both free fatty acid and betahydroxybutyrate. In the diabetic subjects with no demonstrable endogenous insulin secretion, glucagon administration was followed by a rise in plasma free fatty acids and an exaggerated rise in plasma betahydroxybutyrate. The normal control group exhibited a response in betahydroxybutyrate midway between the obese and diabetic groups. These observations support the thesis that the magnitude of endogenous insulin secretion modulates the lipolytic and ketogenic actions of glucagon in man.
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Unger, R.H., Orci, L.: The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet1975 I, 14–16
Gerich, J.E., Tsalikian, E., Lorenzi, M., Karam, J.H., Bier, D.M.: Plasma glucagon and alanine responses to acute insulin deficiency in man. J. clin. Endocr.40, 526–529 (1975)
Alberti, K.G.M.M., Christensen, N.J., Iversen, J., Ørskov, H.: The role of glucagon and other hormones in development of diabetic ketoacidosis. Lancet1975, I 1307–1311
Gerich, J.E., Lorenzi, M., Bier, D.M., Schneider, V., Tsalikian, E., Karam, J.H., Forsham, P.H.: Prevention of human diabetic ketoacidosis by somatostatin. New Engl. J. Med.292, 985–989 (1975)
Liljenquist, J.E., Bomboy, J.D., Lewis, S.B., Sinclair Smith, B.C., Felts, P.W., Lacy, W.W., Crofford, O.B., Liddle, B.W.: Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men. J. clin. Invest.53, 190–197 (1974)
Salter, J.M., Ezrin, C., Laidlaw, J.C., Cornall, A.G.: Metabolic effects of glucagon in human subjects. Metabolism9, 753–768 (1960)
Heimberg, M., Weinstein, I., Kohout, M.: The effects of glucagon, dibutyryl cyclic AMP, and the concentrations of free fatty acids on hepatic lipid metabolism. J. Biochem. (Tokyo)244, 5131–5139 (1969)
McGarry, J.D., Foster, D.W.: Regulation of ketogenesis and clinical aspects of the ketotic state. Metabolism21, 471–489 (1972)
Balasse, E.O., Havel, R.G.: Evidence of an effect of insulin on the peripheral utilization of ketone bodies in dogs. J. clin. Invest.50, 801–817 (1971)
Klimt, C.R., Knatterud, G.L., Meinert, C.L., Prout, T.E.: A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. Diabetes19, 747–783 (1970)
Schade, D.S., Eaton, R.P.: Altered tissue response to glucagon in obesity. J. clin. Endocr.40, 732–735 (1975)
Nakagawa, S., Nakayama, H., Sasaki, T., Yoshino, K., Yu, Y.Y., Shinozaki, K., Aoki, S., Mashimo, K.: A simple method for the determination of serum free insulin levels in insulin treated patients. Diabetes22, 590–600 (1973)
Schade, D.S., Eaton, R.P.: Modulation of free fatty acid metabolism in man I. Diabetes24, 502–509 (1975)
Bahn, A.K.: Basic medical statistics, 1st Ed., p. 134. New York: Grune and Stratton 1972
Lewis, G.P., Mathew, J.: The mobilization of free fatty acids from rabbit adipose tissue. Brit. J. Pharmacol.34, 564–578 (1968)
Lefebvre, P.: The physiological effect of glucagon on fat mobilization. Diabetologia2, 130–134 (1966)
Mahler, R., Stafford, W.S., Tarrant, M.E., Ashmore, J.: The effect of insulin on lipolysis. Diabetes13, 297–302 (1964)
Sarcione, E.J., Back, N., Sokal, J.E., Mehlman, B., Knoblock, E.: Elevation of plasma epinephrine levels produced by glucagon in vivo. Endocrinology72, 523–526 (1963)
Basso, L.V., Havel, R.J.: Hepatic metabolism of free fatty acids in normal and diabetic dogs. J. clin. Invest.49, 537–547 (1970)
Barter, P.J., Nestel, P.J.: Plasma free fatty acid transport during prolonged glucose consumption and its relationship to plasma triglyceride fatty acids in man. J. Lipid Res.13, 483–490 (1972)
Garber, A.J., Menzel, P.H., Boden, G., Owen, O.E.: Hepatic ketogenesis and gluconeogenesis in humans. J. clin. Invest.54, 981–989 (1974)
Heimberg, M., Van Harken, D.R., Weinstein, I., Kohout, M.: Regulatory factors in ketogenesis and in the metabolism of triglycerides by liver. Advanc. Exp. Biol. Med.4, 185–200 (1969)
Pariila, R., Goodman, M.N., Toews, C.J.: Effect of glucagon: Insulin ratios on hepatic metabolism. Diabetes23, 725–731 (1974)
Beatty, C.H., Peterson, R.D., Bocek, R.M., West, E.: Acetoacetate and glucose uptake by diaphragm and skeletal muscle from control and diabetic rats. J. biol. chem.234, 11–15 (1959)
Owen, O.E., Reichard, G.A. Jr., Markusit Boden, G., Mozzoli, M.A., Shuman, C.R.: Rapid intravenous sodium acetoacetate infusions in man. J. clin. Invest.52, 2606–2616 (1973)
Grey, N.M., Karl, I., Kipnis, D.M.: Physiologic mechanisms in the development of starvation ketosis in man. Diabetes24, 10–16 (1975)
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This work was done while D.S. Schade was a Research Associate of the American Diabetes Association
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Schade, D.S., Eaton, R.P. The contribution of endogenous insulin secretion to the ketogenic response to glucagon in man. Diabetologia 11, 555–559 (1975). https://doi.org/10.1007/BF01222106
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DOI: https://doi.org/10.1007/BF01222106