NITRIC-OXIDE DOES NOT INITIATE BUT POTENTIATES GLUCOSE-INDUCED INSULIN-SECRETION IN PANCREATIC BETA-CELLS

The role of nitric oxide (NO) in glucose-induced insulin secretion was studied in pancreatic beta-cells, HIT-T15, A role for NO is suggested since glucose stimulated NO production in a concentration-dependent m anner. N-G-monomethyl-L-arginine, a potent inhibitor of nitric oxide s ynthase, significantly inhibited glucose-induced nitric oxide producti on as well as insulin release in HIT-T15. Furthermore, this inhibitory effect can be reversed by sodium nitroprusside (SNP), a well known NO donor. While SNP alone did not stimulate insulin release, it potentia ted the secretory response of HIT-T15 cells to glucose by approximatel y two-fold. Potentiation by SNP appears to be mediated by NO, since (i ) the potentiation was completely abolished by 10 mu M hemoglobin, a s cavenger of NO; and (ii) was not affected by rhodanese plus sodium thi osulphate, Neither hemoglobin alone nor the combination of rhodanese a nd sodium thiosulphate had any effect on glucose induced insulin relea se, These results are consistent with the hypothesis that glucose-indu ced formation of NO may potentiate the effect of glucose by a positive feedback mechanism. (C) 1998 Academic Press.