Effects of Hepatic Glycogen Content on Hepatic Insulin Action in Humans: Alteration in the Relative Contributions of Glycogenolysis and Gluconeogenesis to Endogenous Glucose Production

Steven Wise, Michael Nielsen, Robert Rizza

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Hepatic glycogen content varies by almost 2-fold during the day, generally increasing from a nadir before breakfast to a peak 4-5 h after supper. To determine whether differences in hepatic glycogen content of this magnitude alter hepatic insulin action, nine subjects were studied on two occasions. On one occasion saline was infused, whereas on the other occasion an infusion of glucose [16.4 μmol/kg lean body mass (-Ibm)·min] was started immediately after supper and continued throughout the night so as to spare hepatic glycogen. The nocturnal glucose infusion resulted in higher (P < 0.05) plasma glucose (6.0 ± 0.1 vs. 5.1 ± 0.1 mmol/L) and insulin (127 ± 38 vs. 49 ± 9 pmol/L) concentrations, and lower (P < 0.05) plasma glucagon concentrations (74 ± 11 vs. 97 ± 20 pg/mL) than did saline infusion. As anticipated, endogenous glucose production (EGP) was substantially lower (P < 0.001) during the glucose than during the saline infusion (7.0 ± 0.9 vs. 19.4 + 1.3 μmol/kg-lbm·min). After discontinuation of the glucose infusion, glucose and insulin concentrations fell to levels that no longer differed from those observed during the saline infusion. In contrast, EGP increased to rates that were higher (P < 0.05) than those observed over the same interval after overnight saline infusion (19.2 ± 1.2 vs. 16.5 ± 0.7 μmol/kg-lbm·min). Despite higher EGP, the rate of incorporation of 14CO2 into glucose was lower (P < 0.001) after glucose than that after saline infusion (9.8 ± 1.2% vs. 24.4 ± 3.0%), implying a reciprocal relationship between hepatic glycogen content and gluconeogenesis. On the other hand, when differences in basal rates were taken into account, insulin-induced suppression of both EGP and incorporation of 14CO2 into glucose did not differ on the two occasions. Thus, whereas hepatic glycogen content influences both the absolute rate of EGP and the percent contribution of gluconeogenesis to EGP, it does not alter hepatic insulin action.

Original languageEnglish (US)
Pages (from-to)1828-1833
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number6
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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