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

Debra Gawler, Graeme Milligan, Allen M. Spiegel, Cecilia G. Unson, Miles D. Houslay

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

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 activity1. 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 activity2 and appear to interact with G-proteins2,3, perhaps by causing phosphorylation of them4. 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 predispostion to infection5. We show here that experimentally-induced type I diabetes leads to the loss of expression of G{ in rat liver. As it has been suggested that Gi may couple receptors to K+- channels6,7 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.

Original languageEnglish (US)
Pages (from-to)229-232
Number of pages4
JournalNature
Volume327
Issue number6119
StatePublished - 1987
Externally publishedYes

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GTP-Binding Proteins
Adenylyl Cyclases
Type 1 Diabetes Mellitus
Second Messenger Systems
Hormones
Insulin
Glucagon
Carrier Proteins
Liver
Insulin Receptor
Cell Surface Receptors
Cyclic AMP
Nervous System
Phosphotransferases
Phosphorylation
Proteins

ASJC Scopus subject areas

  • General

Cite this

Gawler, D., Milligan, G., Spiegel, A. M., Unson, C. G., & Houslay, M. D. (1987). Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes. Nature, 327(6119), 229-232.

Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes. / Gawler, Debra; Milligan, Graeme; Spiegel, Allen M.; Unson, Cecilia G.; Houslay, Miles D.

In: Nature, Vol. 327, No. 6119, 1987, p. 229-232.

Research output: Contribution to journalArticle

Gawler, D, Milligan, G, Spiegel, AM, Unson, CG & Houslay, MD 1987, 'Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes', Nature, vol. 327, no. 6119, pp. 229-232.
Gawler, Debra ; Milligan, Graeme ; Spiegel, Allen M. ; Unson, Cecilia G. ; Houslay, Miles D. / Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes. In: Nature. 1987 ; Vol. 327, No. 6119. pp. 229-232.
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