Desensitization of the inhibitory effect of norepinephrine on insulin secretion from pancreatic islets of exercise-trained rats.
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.
Urano
Yuriko
Y
Department of Kinesiology, Graduate School of Sciene, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
Sakurai
Tomonobu
T
Ueda
Hiroshi
H
Ogasawara
Junetsu
J
Sakurai
Takuya
T
Takei
Megumi
M
Izawa
Tetsuya
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D010805:Physical Conditioning, Animal; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D011518:Proto-Oncogene Proteins; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D012313:RNA; D000242:Cyclic AMP; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498017:Gnai2 protein, rat; D003000:Clonidine; D009638:Norepinephrine