DIABETES ABOLISHES THE GTP-DEPENDENT, BUT NOT THE RECEPTOR-DEPENDENT INHIBITORY FUNCTION OF THE INHIBITORY GUANINE-NUCLEOTIDE-BINDING REGULATORY PROTEIN (G1) ON ADIPOCYTE ADENYLATE-CYCLASE ACTIVITY

Adipocyte membranes from control rats exhibited a functional G(i) (inhibitory guanine-nucleotide-binding protein) activity which could be assessed either by the inhibitory action of low concentrations of guanosine 5-[βγ-imido]triphosphate (p[NH]ppG) upon forskolin-stimulated adenylate cyclase activity or by the inhibitory action of high concentrations of GTP upon isoprenaline-stimulated adenylate cyclase activity. When membranes from animals made diabetic with streptozotocin were used, then both such inhibitory functions of G(i) were abolished. In contrast, receptor-mediated inhibitory responses of G(i), effected by N6-phenylisopropyl (adenosine), prostaglandin E2 or nicotinate, were either unchanged or even apparently more effective in membranes from diabetic animals. Induction of diabetes did not cause any change in the adipocyte plasma membrane levels of the α, GTP-binding subunits of either G(i)1 or G(i)2 or of G(s) (stimulatory guanine-nucleotide-binding protein), but elicited an increase in the level of α-G(i)3. The induction of diabetes reduced the specific activity of adenylate cyclase in adipocyte membranes and enhanced the stimulatory effect of isoprenaline. It is suggested that diabetes causes selective changes in the functioning of G(i) in adipocyte membranes which removes the tonic GTP-dependent inhibitory function of this G-protein.