Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca²⁺ influx through L-type channels in mouse islet β-cells

Abstract

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 NUCB2/nesfatin-1 is localized in pancreatic islet β-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 Ca²⁺ concentration ([Ca²⁺]_i) in single β-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 [Ca²⁺]_i in single β-cells in the presence of 8.3 but not 2.8 mmol/L glucose. The nesfatin-1-induced [Ca²⁺]_i increase and insulin release were inhibited by removal of extracellular Ca²⁺ and by addition of nitrendipine, a blocker of voltage-dependent L-type Ca²⁺ channels. Unexpectedly, the [Ca²⁺]_i responses to nesfatin-1 were unaltered by inhibitors of protein kinase A (PKA) and phospholipase A₂ (PLA₂). These results indicate that nesfain-1 potentiates glucose-induced insulin secretion by promoting Ca²⁺ influx through L-type Ca²⁺ channels independently of PKA and PLA₂ in mouse islet β-cells.