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Nature. 1996 Feb 29;379(6568):840-4.

Insulin action impaired by deficiency of the G-protein subunit G ialpha2.

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Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Program, University Medical Center, SUNY/Stony Brook, New York 11794-8651, USA.


Integration of information between tyrosine kinase and G-protein-mediated pathways is necessary, but remains poorly understood. Here we use cells from transgenic mice harbouring inducible expression of RNA antisense to the gene encoding G ialpha2 to show that G ialpha2 is critical for insulin action. G ialpha2 deficiency in adipose tissue and liver produces hyperinsulinaemia, impaired glucose tolerance and resistance to insulin in vivo. Insulin resistance affects glucose-transporter activity and recruitment, counterregulation of lipolysis, and activation of glycogen synthase, all of which are cardinal responses to insulin. G ialpha2 deficiency increases protein-tyrosine phosphatase activity and attenuates insulin-stimulated tyrosine phosphorylation of IRS (insulin-receptor substrate 1) in vivo. G ialpha2 deficiency creates a model for insulin resistance characteristic of noninsulin-dependent diabetes mellitus (NIDDM), implicating G ialpha2 as a positive regulator of insulin action.

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