Journal of Clinical Endocrinology & Metabolism, Vol 77, 11-15, Copyright © 1993 by Endocrine Society

ARTICLES

Regulation of free fatty acid metabolism by glucagon

MG Carlson, WL Snead and PJ Campbell
Department of Medicine, Vanderbilt University School of Medicine, Nashville 37232-2230.

Glucagon may regulate FFA metabolism in vivo. To test this hypothesis, six healthy male volunteers were infused with somatostatin, to inhibit endogenous hormone secretion, and insulin, glucagon, and GH to replace endogenous secretion of these hormones. In the hypoglucagonemia experiments, the glucagon infusion was omitted, and in the hyperglucagonemic experiments glucagon was infused at 1.3 ng/kg.min, to produce physiological hyperglucagonemia. In two sets of control experiments, glucagon was infused at 0.65 ng/kg.min, in order to maintain peripheral euglucagonemia, and the plasma glucose concentrations were clamped at the levels observed in either the hypo- or hyperglucagonemic experiments. Rates of FFA and glycerol (an index of lipolysis) appearance (Ra) were estimated with the isotope dilution method using [1-14C]palmitate and [2H5] glycerol. Plasma glucagon concentrations decreased during the hypoglucagonemic experiments (85 +/- 12 vs. 123 +/- 22 ng/L, P < 0.05) and increased during the hyperglucagonemic experiments (186 +/- 20 vs. 125 +/- 15 ng/L, P < 0.05), whereas other hormone concentrations remained the same. Hypoglucagonemia resulted in equivalent suppression of FFA Ra (3.7 +/- 0.2 vs. 5.9 vs. 0.3 mumol/kg.min, P < 0.01) and glycerol Ra (1.2 +/- 0.2 vs. 2.2 +/- 0.5 mumol/kg.min, P < 0.05). Similarly, hyperglucagonemia resulted in equivalent stimulation of FFA Ra (5.2 +/- 0.4 vs. 3.7 +/- 0.3 mumol/kg.min, P < 0.05) and glycerol Ra (1.5 +/- 0.3 vs. 1.1 +/- 0.1 mumol/kg.min, P < 0.05). These results indicate that glucagon has a physiological role in the regulation of FFA metabolism in vivo.

This article has been cited by other articles:

				W. Gu, H. Yan, K. A. Winters, R. Komorowski, S. Vonderfecht, L. Atangan, G. Sivits, D. Hill, J. Yang, V. Bi, et al. Long-Term Inhibition of the Glucagon Receptor with a Monoclonal Antibody in Mice Causes Sustained Improvement in Glycemic Control, with Reversible {alpha}-Cell Hyperplasia and Hyperglucagonemia J. Pharmacol. Exp. Ther., December 1, 2009; 331(3): 871 - 881. [Abstract] [Full Text] [PDF]

				S.-S. Chen, T. S. Santomango, P. E. Williams, D. B. Lacy, and O. P. McGuinness Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E1172 - E1178. [Abstract] [Full Text] [PDF]

				I. Quesada, E. Tuduri, C. Ripoll, and A. Nadal Physiology of the pancreatic {alpha}-cell and glucagon secretion: role in glucose homeostasis and diabetes J. Endocrinol., October 1, 2008; 199(1): 5 - 19. [Abstract] [Full Text] [PDF]

				D. S. Houser, C. D. Champagne, and D. E. Crocker Lipolysis and glycerol gluconeogenesis in simultaneously fasting and lactating northern elephant seals Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2007; 293(6): R2376 - R2381. [Abstract] [Full Text] [PDF]

				S.-S. Chen, Y. Zhang, T. S. Santomango, P. E. Williams, D. B. Lacy, and O. P. McGuinness Glucagon chronically impairs hepatic and muscle glucose disposal Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E928 - E935. [Abstract] [Full Text] [PDF]

				R. A. Nafikov, B. N. Ametaj, G. Bobe, K. J. Koehler, J. W. Young, and D. C. Beitz Prevention of Fatty Liver in Transition Dairy Cows by Subcutaneous Injections of Glucagon J Dairy Sci, May 1, 2006; 89(5): 1533 - 1545. [Abstract] [Full Text] [PDF]

				A.-M. Mustonen, S. Saarela, T. Pyykonen, and P. Nieminen Endocrinologic Adaptations to Wintertime Fasting in the Male American Mink (Mustela vison) Experimental Biology and Medicine, October 1, 2005; 230(9): 612 - 620. [Abstract] [Full Text] [PDF]

				S. N. Cheuvront The Zone Diet Phenomenon: A Closer Look at the Science behind the Claims J. Am. Coll. Nutr., February 1, 2003; 22(1): 9 - 17. [Abstract] [Full Text] [PDF]

				S. F. Bernard, M.-A. Thil, and R. Groscolas Lipolytic and metabolic response to glucagon in fasting king penguins: phase II vs. phase III Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R444 - R454. [Abstract] [Full Text] [PDF]

				R. A. Velliquette, R. J. Koletsky, and P. Ernsberger Plasma Glucagon and Free Fatty Acid Responses to a Glucose Load in the Obese Spontaneous Hypertensive Rat (SHROB) Model of Metabolic Syndrome X Experimental Biology and Medicine, March 1, 2002; 227(3): 164 - 170. [Abstract] [Full Text] [PDF]

				R. H. Coker, L. Simonsen, J. Bulow, D. H. Wasserman, and M. Kjar Stimulation of splanchnic glucose production during exercise in humans contains a glucagon-independent component Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E918 - E927. [Abstract] [Full Text] [PDF]

				C. H. Gravholt, N. Møller, M. D. Jensen, J. S. Christiansen, and O. Schmitz Physiological Levels of Glucagon Do Not Influence Lipolysis in Abdominal Adipose Tissue as Assessed by Microdialysis J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2085 - 2089. [Abstract] [Full Text]

				M. Krebs, M. Krssak, P. Nowotny, D. Weghuber, S. Gruber, V. Mlynarik, M. Bischof, H. Stingl, C. Fürnsinn, W. Waldhäusl, et al. Free Fatty Acids Inhibit the Glucose-Stimulated Increase of Intramuscular Glucose-6-Phosphate Concentration in Humans J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2153 - 2160. [Abstract] [Full Text]

				E. Bertin, P. Arner, J. Bolinder, and E. Hagström-Toft Action of Glucagon and Glucagon-Like Peptide-1-(7-36) Amide on Lipolysis in Human Subcutaneous Adipose Tissue and Skeletal Muscle in Vivo J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1229 - 1234. [Abstract] [Full Text]

				N. Flattem, K. Igawa, M. Shiota, M. G. Emshwiller, D. W. Neal, and A. D. Cherrington {alpha}- and {beta}-Cell Responses to Small Changes in Plasma Glucose in the Conscious Dog Diabetes, February 1, 2001; 50(2): 367 - 375. [Abstract] [Full Text]

				A. E. Kitabchi, G. E. Umpierrez, M. B. Murphy, E. J. Barrett, R. A. Kreisberg, J. I. Malone, and B. M. Wall Management of Hyperglycemic Crises in Patients With Diabetes Diabetes Care, January 1, 2001; 24(1): 131 - 153. [Full Text]

				O. P. McGuinness, V. Shau, E. M. Benson, M. Lewis, R. T. Snowden, J. E. Greene, D. W. Neal, and A. D. Cherrington Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog Am J Physiol Endocrinol Metab, October 1, 1997; 273(4): E674 - E681. [Abstract] [Full Text] [PDF]

				M. Gambacciani, M. Ciaponi, B. Cappagli, L. Piaggesi, L. De Simone, R. Orlandi, and A. R. Genazzani Body Weight, Body Fat Distribution, and Hormonal Replacement Therapy in Early Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 414 - 417. [Abstract] [Full Text] [PDF]