Acute Insulin Action Requires Insulin Receptor Kinase Activity: Introduction of an Inhibitory Monoclonal Antibody into Mammalian Cells Blocks the Rapid Effects of Insulin

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-01, Vol.84 (1), p.41-45
• Main Authors: Morgan, David O., Roth, Richard A.
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipose Tissue - metabolism; Animals; Antibodies; Antibodies, Monoclonal; Biological and medical sciences; Cell Line; Cell lines; Cell physiology; CHO cells; Cricetinae; Cricetulus; Cultured cells; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glycogen; Hormonal regulation; Humans; Immunoglobulin G; Insulin; Insulin - pharmacology; Insulin Antibodies; Molecular and cellular biology; Monoclonal antibodies; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Rats; Receptor, Insulin - metabolism; Receptors; Ribosomal Protein S6; Ribosomal Proteins - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.1.41

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 (i) the uptake of 2-deoxyglucose in Chinese hamster ovary cells and freshly isolated rat adipocytes, (ii) ribosomal protein S6 phosphorylation in CHO cells, and (iii) 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 (i) there was no change in phorbol esterstimulated glucose uptake and (ii) 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.