Differential effect of hyperglycemia and hyperinsulinemia on pathways of hepatic glycogen repletion

G. I. Shulman, R. A. DeFronzo, L. Rossetti

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

To delineate the roles of hyperglycemia and insulin on the direct vs. indirect pathways of liver glycogen synthesis, we performed euglycemic (group I; n = 8), hyperglycemic (group II; n = 9), and euglycemic pharmacological hyperinsulinemic clamp studies (120 min) with an infusion of [1-13C]glucose in chronically catheterized conscious rats after a 24-h fast. Portal vein plasma glucose concentrations and portal vein plasma insulin concentrations, respectively, obtained at the end of the study in groups I-III were as follows: group I 110 ± 4 mg/dl, 29 ± 7 ng/ml; group III 219 ± 7 mg/dl, 24 ± 7 ng/ml; and group III 112 ± 9 mg/dl, 174 ± 25 ng/ml. Mean liver glycogen concentrations at the end of the three studies were 0.68 ± 0.07, 1.22 ± 0.08 (P < 0.001 compared with groups I and III), and 0.60 ± 0.17 g/100 g wet wt liver in groups I-III respectively, which yielded hepatic glycogen synthetic rates of 0.16 ± 0.03, 0.41 ± 0.04 (P < 0.001 compared with groups I and III), and 0.13 ± 0.08 μmol glucosyl U·g liver-1·min-1 in groups I-III, respectively. From the enrichments of 13C in the C-1 and C-6 positions of the glucosyl unit in glycogen compared with the enrichment in the C-1 position in portal vein glucose as determined by 13C- and 1H-NMR, the amount of glycogen synthesized by the direct pathway was calculated to be 18 ± 2, 41 ± 3 (P < 0.0001 compared with groups I and III), and 17 ± 3% in groups I-III, respectively. In conclusion, during the insulinized state, hyperglycemia 1) markedly increased the percent of hepatic glycogen synthesized by the direct pathway and 2) played a major role in augmenting hepatic glycogen synthesis.

Original languageEnglish (US)
Pages (from-to)E731-E735
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume260
Issue number5 23-5
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Gluconeogenesis
  • Glucose paradox
  • Nuclear magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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