Inhibition of glycogenolysis and glycogen phosphorylase by insulin and proinsulin in rat hepatocyte cultures.
The inhibitory action of insulin and proinsulin on basal and glucagon-activated glycogenolysis was studied in cultured rat hepatocytes containing [14C]glycogen. Insulin or proinsulin given as sole hormones in the presence of 5 mM glucose decreased basal release of [14C]glucose from [14C]glycogen to 20%. Half-maximal effective concentration of insulin was approximately 0.15 nM and of proinsulin was approximately 5 nM. Inhibition of [14C]lactate release from [14C]glycogen required slightly higher hormone concentrations with a similar difference in potency for insulin and proinsulin. The glucagon-stimulated release of [14C]glucose was completely blocked by insulin or proinsulin with half-maximal effective concentrations of approximately 0.2 and approximately 8 nM, respectively. In contrast, release of [14C]lactate in the presence of glucagon was increased slightly by insulin and proinsulin. Basal and glucagon-activated phosphorylase activity was inhibited by approximately 50% in a dose-dependent manner by both hormones, with differences in potency similar to those for the inhibition of glycogenolysis. These data point to a direct regulatory role of insulin in the control of hepatic glycogen breakdown even when acting as sole hormone. The results do not support the notion of a preferential inhibitory potency of proinsulin on hepatic glycogenolysis.
D000818:Animals; D002478:Cells, Cultured; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D006005:Phosphorylases / Q000378:metabolism*; D011384:Proinsulin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D005934:Glucagon; D011384:Proinsulin; D006005:Phosphorylases; D005947:Glucose