title: Time course of insulin action on tissue-specific intracellular glucose metabolism in normal rats.
abstract: We investigated the time course of insulin action in conscious rats exposed to constant physiological hyperinsulinemia (approximately 100 mU/l) while maintaining euglycemia (approximately 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, Rd), glycolysis (generation of 3H2O in plasma), hepatic glucoses 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 Rd, 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, Rd 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 Rd was explained by parallel increases in glycolysis and glycogen synthesis. From 2 to 4 h the further increase in Rd was entirely due to an increase in glycolysis without change in glycogen synthesis. From 4 to 8 to 12 h of hyperinsulinemia, Rd 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 Rd, 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.
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Koopmans
authors.forename: L
authors.initials: L
authors.lastname: Mandarino
authors.forename: R A
authors.initials: RA
authors.lastname: DeFronzo
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
chemical_list: D007328:Insulin; D008055:Lipids; D006003:Glycogen; D005947:Glucose