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Research Article Free access | 10.1172/JCI118460

The roles of insulin and glucagon in the regulation of hepatic glycogen synthesis and turnover in humans.

M Roden, G Perseghin, K F Petersen, J H Hwang, G W Cline, K Gerow, D L Rothman, and G I Shulman

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Roden, M. in: PubMed | Google Scholar

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Perseghin, G. in: PubMed | Google Scholar

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Petersen, K. in: PubMed | Google Scholar

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Hwang, J. in: PubMed | Google Scholar

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Cline, G. in: PubMed | Google Scholar

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Find articles by Gerow, K. in: PubMed | Google Scholar

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

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Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

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Published February 1, 1996 - More info

Published in Volume 97, Issue 3 on February 1, 1996
J Clin Invest. 1996;97(3):642–648. https://doi.org/10.1172/JCI118460.
© 1996 The American Society for Clinical Investigation
Published February 1, 1996 - Version history
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Abstract

To determine the respective roles of insulin and glucagon for hepatic glycogen synthesis and turnover, hyperglycemic clamps were performed with somatostatin [0.1 micrograms/(kg.min)] in healthy young men under conditions of: (I) basal fasting) portal vein insulinemia-hypoglucagonemia, (II) basal portal vein insulinemia-basal glucagonemia, and (III) basal peripheral insulinemia-hypoglucagonemia. Synthetic rates, pathway (direct versus indirect) contributions, and percent turnover of hepatic glycogen were assessed by in vivo 13C nuclear magnetic resonance spectroscopy during [1-13C]glucose infusion followed by a natural abundance glucose chase in conjunction with acetaminophen to noninvasively sample the hepatic UDP-glucose pool. In the presence of hyperglycemia (10.4 +/- 0.1 mM) and basal portal vein insulinemia (192 +/- 6 pM), suppression of glucagon secretion (plasma glucagon, I:31 +/- 4, II: 63 +/- 8 pg/ml) doubled the hepatic accumulation of glycogen (Vsyn) compared with conditions of basal glucagonemia [I: 0.40 +/- 0.06, II: 0.19 +/- 0.03 mumol/(liter.min): P < 0.0025]. Glycogen turnover was markedly reduced (I: 19 +/- 7%, II: 69 +/- 12%; P < 0.005), so that net rate of glycogen synthesis increased approximately fivefold (P < 0.001) by inhibition of glucagon secretion. The relative contribution of gluconeogenesis (indirect pathway) to glycogen synthesis was lower during hypoglucagonemia (42 +/- 6%) than during basal glucagonemia (54 +/- 5%; P < 0.005). Under conditions of basal peripheral insulinemia (54 +/- 2 pM) and hypoglucagonemia (III) there was negligible hepatic glycogen synthesis and turnover. In conclusion, small changes in portal vein concentrations of insulin and glucagon independently affect hepatic glycogen synthesis and turnover. Inhibition of glucagon secretion under conditions of hyperglycemia and basal concentrations of insulin results in: (a) twofold increase in rate of hepatic glycogen synthesis, (b) reduction of glycogen turnover by approximately 73%, and (c) augmented percent contribution of the direct pathway to glycogen synthesis compared with conditions of basal glucagonemia.

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