L-arginine stimulation of glucose-induced insulin secretion through membrane depolarization and independent of nitric oxide

P Thams, K Capito
1999 European Journal of Endocrinology  
The mechanism of L-arginine stimulation of glucose-induced insulin secretion from mouse pancreatic islets was studied. At 16.7 mmol/l glucose, L-arginine (10 mmol/l) potentiated both phases 1 and 2 of glucose-induced insulin secretion. This potentiation of glucose-induced insulin secretion was mimicked by the membrane depolarizing agents tetraethylammonium (TEA, 20 mmol/l) and K + (60 mmol/l), which at 16.7 mmol/l glucose obliterated L-arginine (10 mmol/l) modulation of insulin secretion. Thus
more » ... in secretion. Thus L-arginine may potentiate glucose-induced insulin secretion by stimulation of membrane depolarization. At 3.3 mmol/l glucose, L-arginine (10 mmol/l) failed to stimulate insulin secretion. In accordance with membrane depolarization by the electrogenic transport of L-arginine, however, L-arginine (10 mmol/l) stimulation of insulin secretion was enabled by the K + channel inhibitor TEA (20 mmol/l), which potentiates membrane depolarization by L-arginine. Furthermore, Larginine (10 mmol/l) stimulation of insulin secretion was permitted by forskolin (10 mmol/l) or tetradecanoylphorbol 13-acetate (0.16 mmol/l), which, by activation of protein kinases A and C respectively sensitize the exocytotic machinery to L-arginine-induced Ca 2+ influx. Thus glucose may sensitize L-arginine stimulation of insulin secretion by potentiation of membrane depolarization and by activation of protein kinase A or protein kinase C. Finally, L-arginine stimulation of glucose-induced insulin secretion was mimicked by N G -nitro-L-arginine methyl ester (10 mmol/l), which stimulates membrane depolarization but inhibits nitric oxide synthase, suggesting that L-arginine-derived nitric oxide neither inhibits nor stimulates insulin secretion. In conclusion, it is suggested that L-arginine potentiation of glucose-induced insulin secretion occurs independently of nitric oxide, but is mediated by membrane depolarization, which stimulates insulin secretion through protein kinase A-and Csensitive mechanisms.
doi:10.1530/eje.0.1400087 pmid:10037257 fatcat:c6oryttjunfiplipku7mxymqp4