Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca~(2+) influx through L-type channels in mouse islet β-cells

摘要

Nucleobindin-2 (NUCB2)-derived nesfatin-1 located in the brain has been implicated in the satiety and control of energy metabolism. Nesfatin-1 is also produced in the periphery and present in the plasma. It has recently been reported that NUCB2esfatin-l is localized in pancreatic islet P-cells in mice and rats and released from islets. However, its function in islets remains largely unknown. This study examined direct effects of nesfatin-1 on insulin release from pancreatic islets and on cytosolic Ca~(2+) concentration ([Ca~(2+)];) in single P-cells from ICR mice. In the presence of 8.3 mmol/L glucose, nesfatin-1 at 10~(-10)-10~(-9) mol/L tended to increase and at 10~(-8) mol/L increased insulin release from isolated islets, while at 2.8 mmol/L glucose nesfatin-1 had no effect. Furthermore, nesfatin-1 at 10~(-10)-10~(-8) mol/L increased [Ca~(2+)]; in single P-cells in the presence of 8.3 but not 2.8 mmol/L glucose. The nesfatin-1-induced [Ca~(2+)]; increase and insulin release were inhibited by removal of extracellular Ca~(2+) and by addition of nitrendipine, a blocker of voltage-dependent L-type Ca~(2+) channels. Unexpectedly, the [Ca~(2+)]i responses to nesfatin-1 were unaltered by inhibitors of protein kinase A (PKA) and phospholipase A_2 (PLA_2). These results indicate that nesfain-1 potentiates glucose-induced insulin secretion by promoting Ca~(2+) influx through L-type Ca~(2+) channels independently of PKA and PLA_2 in mouse islet P-cells.