NG-methyl-L-arginine and somatostatin decrease glucose and insulin and block endothelin-1 (ET-1)-induced insulin release but not ET-1-induced hypoglycemia.
We have previously demonstrated that endothelin-1 (ET-1) increases plasma insulin and decreases blood glucose. The present study was designed to determine if ET-1-induced hypoglycemia occurs in the presence of the insulin secretion inhibitor, somatostatin, and whether ET-1-induced insulin secretion is affected by the nitric oxide synthase I inhibitor, NG-methyl-L-arginine (NMLA), in the anesthetized rat. ET-1 increased plasma insulin and decreased blood glucose in all protocols. Somatostatin alone decreased blood glucose and plasma insulin. Somatostatin blocked ET-1-induced plasma insulin release but did not completely block ET-1-induced hypoglycemia. NMLA alone decreased blood glucose and plasma insulin. NMLA also blocked ET-1-induced insulin release but not ET-1-induced hypoglycemia. The present study confirms our previous finding that ET-1 decreases blood glucose and increases plasma insulin. Because hypoglycemia occurs during insulin inhibition with somatostatin, the present study suggests that ET-1-induced hypoglycemia is partially caused by non-insulin-mediated mechanisms. Because insulin secretion is blocked by nitric oxide synthase I inhibitor, NMLA, the present study suggests that ET-1-induced insulin release may be mediated by production of nitric oxide.
Zimmerman
R S
RS
Alton Oshsner Medical Foundation, New Orleans, LA, USA.
Maymind
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D007003:Hypoglycemia / Q000139:chemically induced* / Q000517:prevention & control; D007328:Insulin / Q000097:blood*; D007329:Insulin Antagonists / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D001786:Blood Glucose; D016232:Endothelins; D007328:Insulin; D007329:Insulin Antagonists; D019323:omega-N-Methylarginine; D013004:Somatostatin; D001120:Arginine