Metabolic actions of insulin-like growth factor-I in cultured hepatocytes from adult rats.
Short-term and long-term regulation of hepatic carbohydrate metabolism by insulinlike growth factor-I was studied in primary cultures of adult rat hepatocytes and compared with the metabolic potency of insulin. Insulinlike growth factor-I stimulated the formation of [14C]lactate from [14C]glucose up to three-fold with a half-maximally effective concentration of approximately 50 nmol/L. Basal glycogenolysis was inhibited by about 20%, and glucagon-activated glycogenolysis was blocked completely by insulinlike growth factor-I with half-maximally effective concentrations of about 1.5 to 2 nmol/L. The activity of the key glycolytic enzymes glucokinase and pyruvate kinase were induced twofold. The glucagon-dependent induction of phosphoenolpyruvate carboxykinase--the key gluconeogenic enzyme--was antagonized with a half-maximally effective concentration of about 5 nmol/L. This inhibition of the glucagon-dependent induction of the enzyme was accompanied by a similar reduction of the increase in phosphoenolpyruvate carboxykinase-mRNA level as assessed by Northern blot analysis. The potency of insulinlike growth factor-I at half-maximally effective concentrations was approximately 2% to 4% that of insulin. Because binding studies demonstrated a comparably low affinity of insulinlike growth factor-I to the insulin receptor, it is suggested that in adult liver--in contrast to fetal and regenerating liver--insulinlike growth factor-I could exert short-term and long-term metabolic effects on parenchymal cells only through interaction with the insulin receptor.
Hartmann
H
H
Department of Medicine, University of Göttingen, Federal Republic of Germany.
Schmitz
F
F
Christ
B
B
Jungermann
K
K
Creutzfeldt
W
W
D000818:Animals; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D005941:Glucokinase / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D005934:Glucagon; D005941:Glucokinase; D011770:Pyruvate Kinase