Insulin-like action of proinsulin on rat liver carbohydrate metabolism in vitro.
Short-term effects of human proinsulin on metabolic rates and its long-term action on enzyme induction were studied in primary cultures of rat hepatocytes and in the perfused rat liver, and compared with the effects of bovine insulin. In the perfused rat liver, proinsulin decreased the glucagon-dependent increase of glycogenolysis. The action of 0.5 nM glucagon was almost completely suppressed by 100 nM proinsulin. Proinsulin and insulin showed similar potency. In cultured rat hepatocytes, proinsulin stimulated glycolysis up to fivefold with a half-maximal effective dose of 30 nM. Proinsulin induced the key glycolytic enzymes glucokinase and pyruvate kinase by twofold and antagonized the glucagon-dependent induction of phosphoenolpyruvate carboxykinase with a half-maximal effective dose at 3 nM. For the effects in cultured hepatocytes, about 100-fold higher concentrations of proinsulin than of insulin were required.
D000818:Animals; D050260:Carbohydrate Metabolism; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D005934:Glucagon / Q000037:antagonists & inhibitors; D005941:Glucokinase / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010477:Perfusion; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000096:biosynthesis; D011384:Proinsulin / Q000494:pharmacology*; D011770:Pyruvate Kinase / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007328:Insulin; D008112:Liver Glycogen; D005934:Glucagon; D011384:Proinsulin; D005941:Glucokinase; D011770:Pyruvate Kinase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)