Time course of insulin action on tissue-specific intracellular glucose metabolism in normal rats

Sietse J. Koopmans, Lawrence Mandarino, Ralph A. DeFronzo

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19 Scopus citations


We investigated the time course of insulin action in conscious rats exposed to constant physiological hyperinsulinemia (~100 mU/l) while maintaining euglycemia (~100 mg/dl) for 0, 0.5, 2, 4, 8, or 12 h. [3- 3H]glucose was infused to quantitate whole body glucose disposal (rate of disappearance, R(d)), glycolysis (generation of 3H2O in plasma), hepatic glucose production (HGP), and skeletal muscle and liver glycogen synthesis ([3-3H]glucose incorporation into glycogen and time-dependent change in tissue glycogen concentration). The basal R(d), which equals HGP, was 6.0 ± 0.3 mg · kg-1 · min-1. With increased duration of hyperinsulinemia from 0 to 0.5 to 2 to 4 h, R(d) increased from 6.0 ± 0.3 to 21.0 ± 1.1 to 24.1 ± 1.5 to 26.6 ± 0.6 mg · kg-1 · min-1 (P < 0.05 for 2 and 4 h vs. 0.5 h). During the first 2 h the increase in R(d) was explained by parallel increases in glycolysis and glycogen synthesis. From 2 to 4 h the further increase in R(d) was entirely due to an increase in glycolysis without change in glycogen synthesis. From 4 to 8 to 12 h of hyperinsulinemia, R(d) decreased by 19% from 26.6 ± 0.6 to 24.1 ± 1.1 to 21.6 ± 1.8 mg · kg-1 · min-1 (P < 0.05 for 8 h vs. 4 h and 12 h vs. 8 h). The progressive decline in R(d), in the face of constant hyperinsulinemia, occurred despite a slight increase (8-14%) in glycolysis and was completely explained by a marked decrease (64%) in muscle glycogen synthesis. In contrast, liver glycogen synthesis increased fourfold, indicating an independent regulation of muscle and liver glycogen synthesis by long-term hyperinsulinemia. In the liver, during the entire 12-h period of insulin stimulation, the contribution of the direct (from glucose) and the indirect (from C-3 fragments) pathways to net glycogen formation remained constant at 77 ± 5 and 23 ± 5%, respectively. HGP remained suppressed throughout the 12-h period of hyperinsulinemia.

Original languageEnglish (US)
Pages (from-to)E642-E650
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number4 37-4
StatePublished - Apr 1998


  • Glycogen synthesis
  • Glycolysis
  • Hepatic glucose production
  • Insulin resistance
  • Lipid metabolism

ASJC Scopus subject areas

  • General Medicine


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