Acute insulin action requires insulin receptor kinase activity: introduction of an inhibitory monoclonal antibody into mammalian cells blocks the rapid effects of insulin.
The role of the insulin receptor tyrosine kinase (protein-tyrosine kinase, EC 2.7.1.112) in various rapid insulin effects was studied by injecting four different cell types (by osmotic lysis of pinocytotic vesicles) with a monoclonal antibody that specifically inhibits the kinase activity of the insulin receptor and the closely related receptor for insulin-like growth factor (IGF)-I. Injection of this inhibitory antibody resulted in a decreased ability of insulin to stimulate the uptake of 2-deoxyglucose in Chinese hamster ovary cells and freshly isolated rat adipocytes, ribosomal protein S6 phosphorylation in CHO cells, and glycogen synthesis in the human hepatoma cell line HepG2. The ability of insulin, IGF-I, and IGF-II to stimulate glucose uptake in TA1 mouse adipocytes was also inhibited. Studies with CHO cells demonstrated that these effects of the inhibitory antibody were specific, since there was no change in phorbol ester-stimulated glucose uptake and injection of a noninhibiting antibody to the kinase had no effect on insulin action. These studies indicate that the tyrosine kinase activity of the insulin receptor is important in mediating several rapid insulin effects in a variety of different cell types.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G; D007328:Insulin / Q000494:pharmacology*; D007330:Insulin Antibodies; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose