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 (> or =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 micromol/L)-induced inhibition of insulin secretion was reversed by the blockade of the alpha(2)-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 alpha(2)-adrenergic receptor either per islet or per protein of islet crude membrane. However, exercise training significantly reduced the protein expression of G alpha i-2 without change in G alpha i-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 Ca(2+)-free conditions. Thus, exercise training appears to provoke a decreased expression of G alpha i-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.
Subject(s)
Blood Glucose/metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Insulin/metabolism , Islets of Langerhans/metabolism , Norepinephrine/physiology , Physical Conditioning, Animal , Proto-Oncogene Proteins/metabolism , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Blotting, Western , Clonidine/pharmacology , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Down-Regulation , GTP-Binding Protein alpha Subunit, Gi2 , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , In Vitro Techniques , Insulin Secretion , Male , Norepinephrine/pharmacology , Proto-Oncogene Proteins/genetics , RNA/analysis , Rats , Rats, Wistar , Receptors, Adrenergic, alpha-2/drug effects , Receptors, Adrenergic, alpha-2/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Yohimbine/pharmacologyABSTRACT
It is well known that glucose-stimulated insulin secretion (GSIS) decreases after exercise training. In the present study, we investigated the effects of exercise training (9 weeks of running) on the activity of glucokinase (GK), the production of nitric oxide (NO), and the protein expressions of both glucose transporter-2 (GLUT-2) and NO synthase (NOS) in rat pancreatic islets. Exercise training significantly reduced GSIS, with decreases in GK activity and GLUT-2 protein expression. The NO releases and cGMP contents were higher in the islets of trained rats than in those of control rats. Exercise training enhanced cNOS activity, the protein expression of both neuronal nitric oxide synthase (nNOS) and calmodulin, and NADPH-cytochrome c reductase activity in the homogenates of islets. Thus, exercise training-induced reduction of GSIS would result from, at least in part, decreases in both glucose entry and the first step in glycolytic utilization of glucose. Moreover, exercise training could enhance the protein expression of nNOS, which in turn enhances two catalytic activities of nNOS, an NO production and a cytochrome c reductase activity.
