Diabetes abolishes the GTP-dependent, but not the receptor-dependent inhibitory function of the inhibitory guanine-nucleotide-binding regulatory protein (Gi) on adipocyte adenylate cyclase activity.
Adipocyte membranes from control rats exhibited a functional Gi (inhibitory guanine-nucleotide-binding protein) activity which could be assessed either by the inhibitory action of low concentrations of guanosine 5-[beta gamma-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 Gi were abolished. In contrast, receptor-mediated inhibitory responses of Gi, 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 alpha, GTP-binding subunits of either Gi1 or Gi2 or of Gs (stimulatory guanine-nucleotide-binding protein), but elicited an increase in the level of alpha-Gi3. 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 Gi in adipocyte membranes which removes the tonic GTP-dependent inhibitory function of this G-protein.
Strassheim
D
D
Institute of Biochemistry, University of Glasgow, Scotland, U.K.
Milligan
G
G
Houslay
M D
MD
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006160:Guanosine Triphosphate / Q000502:physiology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009525:Niacin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000502:physiology; D018078:Receptors, Prostaglandin E; D011983:Receptors, Purinergic / Q000502:physiology
D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D011983:Receptors, Purinergic; D005576:Colforsin; D009525:Niacin; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol