Involvement of cyclic guanosine 3[prime ],5[prime ]-monophosphate in nitric oxide-induced glucagon secretion from pancreatic alpha cells

Abstract 

It has been reported that nitric oxide (NO) is a positive modulator of glucagon release. The involvement of cyclic guanosine 3[prime ],5[prime ]-monophosphate (cGMP) in NO-induced glucagon secretion and the possible role of NO in glucagon release induced by l-arginine were investigated in mouse clonal [alpha ]-cell line clone 6 ([alpha ]TC6) cells, which predominantly secrete glucagon. NOC12, an NO donor, elicited an increase in glucagon release from [alpha ]Tc6 cells in perifusion and static incubation. An inhibitor of cGMP-dependent protein kinase inhibited NOC12-induced glucagon release. NOC12 (1 mmol/L) also increased the cellular level of cGMP. In addition, a permeable cGMP agonist increased glucagon release. l-arginine (15 mmol/L) increased perifusate concentrations of glucagon and nitrite in [alpha ]Tc6 cells, which were inhibited by N^G-nitro-L-arginine methyl ester. NO synthase (NOS) activity was shown in [alpha ]Tc6 cells by l-citrulline formation assay. Our present findings suggest that NO plays a stimulating role in glucagon release from the [alpha ] cells, and that a cGMP-dependent pathway is involved in NO action. These findings also provide further evidence that l-arginine might play a stimulating role in regulating glucagon secretion, at least partly, through generation of NO in the islets.

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