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 ins...

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Bibliographic Details
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
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.84.1.41