Ghrelin对离体大鼠胰岛分泌胰岛素的影响及其机制

目的 观察外源性Ghrelin对胰岛素分泌和胰岛内向整流钾通道(Kir6.2)表达的影响.方法 Wistar大鼠按10 nmoL/kg的剂量予Ghrelin腹腔注射2周后,分离胰岛进行胰岛素释放实验,分离β细胞检测静息膜电位;检测胰岛Kir6.2 mRNA和蛋白表达变化.结果 在11.1、16.7mmol/L葡萄糖刺激下,对照组的胰岛素释放分别为22.5、43.5 uIU/胰岛/h,Ghrelin组为15.2、30.1uIU/胰岛/h,较对照组显著降低(P＜0.05).对照组β细胞的静息膜电位为(-73.2±24.8)mV,Ghrelin组为(-95.4±33.7)mV,较对照组显著降低(P＜0.05).而Ghrelin组Kir6.2表达显著高于对照组(P＜0.05).结论 Ghrelin与其受体结合后抑制胰岛素分泌,其机制可能与上调Kir6.2表达,使β细胞兴奋性降低有关.

Abstract：

Objective To investigate the influence of ghrelin administration on the insulin secretion, and the expression of Kir6. 2 channels in islets. Methods Ghrelin was intraperitoneally administrated in Wistar rats at the doses 10 nmol/kg every day for 2 weeks. Islets were isolated for insulin release experiments. Single β cells were isolated for electrophysiological experiments. Meanwhile, the expression levels of Kir6. 2 mRNA and protein in islets were detected. Results At 11. 1 and 16. 7 mmol/L glucose,the levels of insulin release in control group were 22. 5 and 43.5 uIU/islet per h, and those in ghrelin-treated group were 15. 2 and 30. 1 uIU/islet per h (P ＜0. 05 ). In control group, the resting membrane potential reached ( - 73.2 ± 24. 8 ) mV, but in ghrelin-treated group, it was hyperpolarized to ( - 95.4 ± 33.7 )mV ( P ＜ 0. 05 ). The Kir6. 2 expression levels were significantly up-regulated by ghrelin ( P ＜ 0. 05 ).Conclusion Ghrelin via pancreatic GHSR up-regulates the Kir6. 2 expression in islets, hyperpolarizing the resting membrane potential, and resulting in the inhibition of insulin release.

Influence and mechanism of ghrelin on insulin release in isolated rat islets

Objective To investigate the influence of ghrelin administration on the insulin secretion, and the expression of Kir6. 2 channels in islets. Methods Ghrelin was intraperitoneally administrated in Wistar rats at the doses 10 nmol/kg every day for 2 weeks. Islets were isolated for insulin release experiments. Single β cells were isolated for electrophysiological experiments. Meanwhile, the expression levels of Kir6. 2 mRNA and protein in islets were detected. Results At 11. 1 and 16. 7 mmol/L glucose,the levels of insulin release in control group were 22. 5 and 43.5 uIU/islet per h, and those in ghrelin-treated group were 15. 2 and 30. 1 uIU/islet per h (P ＜0. 05 ). In control group, the resting membrane potential reached ( - 73.2 ± 24. 8 ) mV, but in ghrelin-treated group, it was hyperpolarized to ( - 95.4 ± 33.7 )mV ( P ＜ 0. 05 ). The Kir6. 2 expression levels were significantly up-regulated by ghrelin ( P ＜ 0. 05 ).Conclusion Ghrelin via pancreatic GHSR up-regulates the Kir6. 2 expression in islets, hyperpolarizing the resting membrane potential, and resulting in the inhibition of insulin release.