Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes

Many cell-surface receptors for hormones appear to exert their effects on target cells by interacting with specific guanine nucleotide binding regulatory proteins (G-proteins) which couple receptors to their second-messenger signal generation systems. A common intracellular second messenger, which i...

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Bibliographic Details
Published in:Nature (London) 1987-05, Vol.327 (6119), p.229-232
Main Authors: GAWLER, D, MILLIGAN, G, SPIEGEL, A. M, UNSON, C. G, HOUSLAY, M. D
Format: Article
Language:English
Subjects:
Adenosine Diphosphate Ribose - metabolism
Adenylate Cyclase Toxin
Adenylyl Cyclase Inhibitors
Adenylyl Cyclases - metabolism
Animals
Biological and medical sciences
Cell Membrane - metabolism
Colforsin - pharmacology
Diabetes Mellitus, Experimental - physiopathology
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Glucagon - pharmacology
GTP-Binding Proteins - physiology
Guanylyl Imidodiphosphate - pharmacology
Liver - metabolism
Medical sciences
Rats
Virulence Factors, Bordetella - pharmacology
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Summary:Many cell-surface receptors for hormones appear to exert their effects on target cells by interacting with specific guanine nucleotide binding regulatory proteins (G-proteins) which couple receptors to their second-messenger signal generation systems. A common intracellular second messenger, which is used by many hormones, is cyclic AMP. This is produced by adenylate cyclase, whose activity is controlled by two G-proteins, Gs which mediates stimulatory effects and Gi inhibitory effects on adenylate cyclase activity. In liver, the hormone glucagon increases intracellular cAMP concentrations by activating adenylate cyclase by a Gs-mediated process. This effect of glucagon is antagonised by the hormone insulin, although the molecular mechanism by which insulin elicits its actions is obscure. However, insulin receptors exhibit a tyrosyl kinase activity and appear to interact with G-proteins, perhaps by causing phosphorylation of them. In type I diabetes, circulating insulin levels are abnormally low, giving rise to gross perturbations of metabolism as well as to a variety of complications such as ionic disturbances, neuropathies of the nervous system, respiratory and cardiovascular aberrations and predisposition to infection. We show here that experimentally-induced type I diabetes leads to the loss of expression of Gi in rat liver. As it has been suggested that Gi may couple receptors to K+-channels as well as mediating the inhibition of adenylate cyclase, aberrations in the control of expression of this key regulatory protein in type I diabetes may be expected to lead to pleiotropic effects.
ISSN:0028-0836
1476-4687
DOI:10.1038/327229a0