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PMID: 8609218 Published · ppublish English Clinical Trial Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 97 ·No. 3 ·1996-02-01 ·Pages 642-8

Roden M, Perseghin G, Petersen KF, Hwang JH, Cline GW, Gerow K, Rothman DL, Shulman GI

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.

MeSH Terms
Adult Amino Acids/blood C-Peptide/blood Fatty Acids, Nonesterified/blood Gastrointestinal Agents/metabolism Glucagon/blood,metabolism Glucose/metabolism Glucose Clamp Technique Glycogen/metabolism Humans Hyperglycemia Hypoglycemic Agents/metabolism Insulin/blood,metabolism Lactates/blood Lactic Acid Liver/metabolism Male Models, Biological
Chemicals
Amino Acids C-Peptide Fatty Acids, Nonesterified Gastrointestinal Agents Hypoglycemic Agents Insulin Lactates Lactic Acid Glycogen Glucagon Glucose
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Roden M
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Perseghin G
Petersen K F
Hwang J H
Cline G W
Gerow K
Rothman D L
Shulman G I
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118460
Published
1996-02-01
Pages
642-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507099
Subset
IM
Grants
NIDDK NIH HHS · P30 DK-45735 · United States
NIDDK NIH HHS · R01 DK040936 · United States
NIDDK NIH HHS · R01 DK-49230 · United States
NINDS NIH HHS · R29 NS-32126 · United States
NCRR NIH HHS · M01 RR-00125 · United States
External Links
PubMed source DOI: 10.1172/JCI118460 PMC Full Text View journal details
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