THE REVERSAL EFFECT OF INSULIN ON DIABETES-INDUCED ALTERATIONS IN BETA-ADRENERGIC AND MUSCARINIC RECEPTORS IN RAT PROSTATE

Previous studies from our laboratory demonstrated that 8 weeks after t he induction of diabetes by the administration of streptozotocin (STZ) there was a downregulation of beta adrenergic and muscarinic choliner gic receptors in rat prostate, and that early insulin treatment (start ed 3 days after the onset of diabetes) prevented these alterations fro m occurring. In the present study, the effects of later insulin treatm ent (started 8 weeks after the onset of diabetes) on the reversibility of diabetes-induced alterations in beta adrenergic and muscarinic rec eptors in rat prostate were investigated. Three groups of rats were ma intained for 16 weeks: 1) diabetics, 2) insulin-treated diabetics (sub cutaneously injected with 5 to 8 U per day starting 8 weeks after the onset of diabetes) and 3) age matched controls. Binding studies with [ H-3]dihydroalprenolol (DHA) and [H-3]quinuclidinyl benzilate (QNB) sho wed a significantly lower density of beta adrenergic and muscarinic ch olinergic receptors in the diabetic rat prostate than in prostate from either controls or insulin-treated diabetic animals. Inhibition of [H -3]DHA binding by isoproterenol, a beta adrenergic agonist, and bindin g of [H-3]QNB by carbachol, a muscarinic agonist, indicated the presen ce of low and high affinity agonist binding sites for each receptor. T he relative proportion of high affinity to total binding sites as well as the low and high affinity constants were similar in all groups. Th ese data indicate that insulin treatment, begun 8 weeks after the onse t of diabetes, can reverse the diabetes-induced downregulation of both beta adrenergic and muscarinic cholinergic receptors in STZ-diabetic rat prostates.