Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca2+ influx through L-type channels in mouse islet β-cells
Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca2+ influx through L-type channels in mouse islet β-cells
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DOI：
10.1507/endocrj.k11e-056
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发表时间：
2011-04-20
影响因子：
2
通讯作者：
Yada, Toshihiko
中科院分区：
文献类型：
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作者：
Nakata, Masanori;Manaka, Kazunori;Yada, Toshihiko
位于大脑中的核结合素-2（NUCB 2）衍生的nesfatin-1与饱腹感和能量代谢的控制有关。奈脂素-1也在外周产生并存在于血浆中。最近报道，NUCB 2/nesfatin-1定位于小鼠和大鼠的胰岛β细胞中，并从胰岛释放。然而，其在胰岛中的功能在很大程度上仍然未知。本研究检测了nesfatin-1对胰岛释放胰岛素和ICR小鼠单个β细胞胞浆Ca 2+浓度（[Ca 2 +]（i））的直接影响。在8.3mmol/L葡萄糖存在下，10（-10）~ 10（-9）mol/L的nesfatin-1有增加胰岛分泌胰岛素的趋势，10（-8）mol/L的nesfatin-1有增加胰岛分泌胰岛素的趋势，2.8mmol/L的葡萄糖nesfatin-1对胰岛分泌胰岛素无影响。10（-10）~ 10（-8）mol/L的nesfatin-1可增加单个P细胞内[Ca ~（2+）]（i），但对2.8mmol/L葡萄糖无明显影响。nesfatin-1诱导的[Ca ~（2+）]（i）升高和胰岛素释放可被细胞外Ca ~（2+）清除和电压依赖性L型Ca ~（2+）通道阻滞剂尼群地平抑制。出乎意料的是，蛋白激酶A（PKA）和磷脂酶A（2）（PLA（2））的抑制剂对nesfatin-1的[Ca 2 +] i反应没有改变。这些结果表明，nesfain-1通过促进小鼠胰岛β细胞中的L型Ca 2+通道的Ca 2+内流而增强葡萄糖诱导的胰岛素分泌，而不依赖于PKA和PLA（2）。
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 beta-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 beta-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 P-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+]; 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 Ca2+ influx through L-type Ca2+ channels independently of PKA and PLA(2) in mouse islet beta-cells.