G-proteins and beta-adrenergic stimulation of adenylate cyclase activity in the diabetic rat prostate.

Abstract

The consequences of experimental diabetes on membrane lipids, beta-adrenergic stimulation of adenylate cyclase activity, and G-protein levels in the prostate gland are not defined. Prostatic membranes from control and streptozotocin (STZ)-diabetic rats were used to study adenylate cyclase stimulation as well as for immunodetection of stimulatory (alpha s) and inhibitory (alpha i) G-protein subunits. Changes in membrane lipid composition were estimated by [1-14C] acetate incorporation into lipid subclasses. The efficacy of isoproterenol on stimulation of adenylate cyclase activity and the levels of alpha s, alpha i1/2, and alpha i3/0 G-protein subunits were drastically reduced in prostatic membranes from STZ-diabetic rats. Insulin treatment of diabetic rats tended to normalize G-protein levels, but it was ineffective on the poor adenylate cyclase response to isoproterenol or forskolin. However, it prevented enzyme desensitization to vasoactive intestinal peptide. The pattern of [1-14C] acetate incorporation into lipid subclasses did not vary with diabetes or insulin treatment. STZ-induced diabetes results in desensitization for the beta-adrenergic response of adenylate cyclase, as supported by previous data on the low density of beta-adrenergic receptors and the present results on the general decrease of Gs and Gi proteins levels and even of the enzyme itself in the diabetic rat prostate.