Involvement of cyclic guanosine 3',5'-monophosphate in nitric oxide-induced glucagon secretion from pancreatic alpha cells.
It has been reported that nitric oxide (NO) is a positive modulator of glucagon release. The involvement of cyclic guanosine 3',5'-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.
Mori
T
T
First Division, Department of Medicine, Shimane Medical University, Izumo, Japan.
Murakami
Y
Y
Koshimura
K
K
Hamaguchi
K
K
Kato
Y
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology*
C429686:3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene; D020030:Nitric Oxide Donors; D014226:Triazenes; D009569:Nitric Oxide; D005934:Glucagon; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester