title: Inhibition of hepatic glucose production by insulin in vivo in rats: contribution of glycolysis.
abstract: The action of insulin on hepatic glucose production (HGP) has been studied in fed anesthetized rats during a euglycemic hyperinsulinemic clamp. At the end of the clamp, the liver was rapidly removed, frozen, and enzyme activities and metabolites were measured. When insulin totally suppressed HGP, it did not modify glycogen phosphorylase or synthase activity, nor did it "spare" or increase glycogen content. Insulin decreased glucose 6-phosphate while increasing glycolytic intermediates (fructose 1,6-bisphosphate, alpha-glycerophosphate, lactate, and pyruvate) as well as fructose 2,6-bisphosphate, the potent effector of 6-phosphofructo-1-kinase. Insulin also increased pyruvate kinase activity of low substrate concentration. Lipogenesis measured with 3H2O incorporation into fatty acids was increased four-to fivefold by insulin. The data suggest that in normal rat liver, when glycemia is maintained at constant basal level, insulin promotes no change in glycogen metabolism, whereas the hormone stimulates the glycolytic pathway. This action contributes to the suppression of hepatic glucose production observed after the addition of the hormone.
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000096:biosynthesis; D005635:Fructosediphosphates / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D006006:Glycogen Synthase / Q000378:metabolism; D006019:Glycolysis; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005635:Fructosediphosphates; D007328:Insulin; C027652:fructose 2,6-diphosphate; D000242:Cyclic AMP; D006005:Phosphorylases; D006006:Glycogen Synthase; D014532:Uridine Diphosphate Glucose