Altered G-protein expression and adenylate cyclase activity in platelets of non-insulin-dependent diabetic (NIDDM) male subjects

Abstract

Adenylate cyclase activity and levels of guanine nucleotide regulatory proteins (G-proteins) were compared in platelets from normal and non-insulin-dependent diabetic (NIDDM) male subjects. Whilst no differences were noted in basal and NaF-stimulated cyclase activities the degree of stimulation achieved by both forskolin and prostaglandin, E 1 was lower by some 34 and 52% respectively, in platelet membranes from diabetic subjects compared with those from normal control subjects. Altered α 1-adrenoceptor-mediated inhibition of prostaglandin E 1-stimulated adenylate cyclase activity was evident; it being some 34% lower in platelet membranes from diabetic subjects compared to controls. Analysis of G-protein α-subunits, using specific anti-peptide antisera, wshowed that platelets from all subjects exhibited the G i-2 and G i-3, but not the G i-1 forms of the inhibitory G-protein ‘G i’ and all expressed the 42 kDa species of α-subunits of the stimulatory G-protein G s. Whilst platelets of siabetic subjects had levels of G s whihch were comparable to those found in control subjects their levels of G i-2 and G i-3 were some 49 and 75%, respectively, of those found in platelets from control subjects. Its is suggested that changes in adenylate cyclase functioning and G-protein expression may contribute to altered platelet functioning in non-insulin-dependent diabetic subjects.