N^G-Methyl-l-arginine and somatostatin decrease glucose and insulin and block endothelin-1 (ET-1)-induced insulin release but not ET-1-induced hypoglycemia☆☆☆

Abstract 

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, N^G-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 the nitric oxide synthase I inhibitor, NMLA, the present study suggests that ET-1- induced insulin release may be mediated by production of nitric oxide.

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