Nitric oxide-cyclic GMP system potentiates glucose-induced rise in cytosolic Ca~(2+) concentration in rat pancreatic #beta#-cells

摘要

Involvement of nitric oxide (NO) in the regulation of insulin secretion from pancreatic #beta#-cells was investigated by measuring cytosolic Ca~(2+) concentration ([Ca~(2+)]_i) in isolated rat pancreatic #beta#-cells. At 7.0 mM glucose, L-arginine (0.1 mM) elevated [Ca~(2+)]_i in about 50% of the #beta#-cells examined. The response was partially inhibited by an NO synthase inhibitor, N~G-monomethyl-L-arginine (L-NMA; 0.1 mM), suggesting that part of the response was mediated by the production of NO from L-arginine. D-Arginine at higher concentrations (3 or 10 mM) also increased [Ca~(2+)]_i at 7.0 mM glucose however, the response was not affected by L-NMA (0.1 mM). Similar [Ca~(2+)]_i elevation was produced by NO (10 nM) and sodium nitroprusside (SNP; 10#mu#M) at 7.0 mM glucose. The SNP-induced increase in [Ca~(2+)]_i was abolished by nicardipine (1 #mu#M), suggesting that the [Ca~(2+)]_i response is mediated by Ca~(2+) influx through L-type voltage-operated Ca~(2+) channels. In the presence of oxyhemoglobin (1 #mu#M), the [Ca~(2+)]_i elevation induced by NO (10 nM) was abolished. Neither degradation products of NO, NO_2 nor NO_3, caused any changes in [Ca~(2+)]_i. 8-Bromo-cyclic GMP (8-Br-cGMP; 3 mM) and atrial natriuretic peptide (0.1 #mu#M) elevated [Ca~(2+)]_i at 7.0 mM glucose. We conclude that NO, which is produced from L-arginine in pancreatic islets, facilitates glucose-induced [Ca~(2+)]_i increase via the elevation of cGMP in rat pancreatic #beta#-cells. NO-cGMP system may physiologically regulate insulin secretion from pancreatic #beta#-cells.