Desensitization of the inhibitory effect of norepinephrine on insulin secretion from pancreatic islets of exercise-trained rats

Abstract

The effect of exercise training (9 weeks of running) on norepinephrine-induced inhibition of insulin secretion was examined in rat islets. Insulin secretions from islets in the presence of glucose (≥5.5 mmol/L) were significantly lower in trained (TR) than in control rats (CR). Norepinephrine inhibited 5.5 mmol/L glucose-stimulated insulin secretions and cyclic adenosine monophosphate (cAMP) contents in a dose-dependent manner in CR. Norepinephrine (10 μmol/L)-induced inhibition of insulin secretion was reversed by the blockade of the α2-adrenergic receptor in CR, but not in TR. Exercise training substantially shifted the dose-dependent curve for clonidine-induced inhibition of insulin secretions and that of cAMP contents to the right. Exercise training did not alter the density of the α2-adrenergic receptor either per islet or per protein of islet crude membrane. However, exercise training significantly reduced the protein expression of Gαi-2 without change in Gαi-2 mRNA. In CR but not in TR, norepinephrine significantly inhibited insulin secretions elicited by a combination of high glucose, a protein kinase C activator, and an adenylate cyclase activator under Ca2+-free conditions. Thus, exercise training appears to provoke a decreased expression of Gαi-2 protein. This, at least in part, results in loss of the inhibitory effect of norepinephrine either on cAMP content or on insulin secretion at the post-calcium events in stimulus-secretion coupling, which, in turn, leads to the blunted inhibitory effects of norepinephrine on insulin secretion.