中文摘要：

目的探讨增食欲素A（OrexinA）通过增食欲素受体1（OX1R）和AKT／PKB信号传导途径对胰岛细胞增殖的干预效应。方法体外培养的大鼠INS-1胰岛素瘤细胞暴露于不同浓度的OrexinA，OX1R拮抗剂（SB334867）、P13K拮抗剂（渥曼青霉素）和AKT拮抗剂（PF-04691502）干预OrexinA的作用，测定INS-1的细胞增殖、凋亡、胰岛素分泌、OX1R蛋白活性及AKT蛋白磷酸化水平。结果OrexinA（10^-10-10^-6mol／L）可刺激INS-1细胞的增殖和活化，防止细胞凋亡，并增加胰岛素的分泌；OrexinA（10^-10-10^-6mol／L）增强了INS-1细胞内AKT的磷酸化，SB334867（10^-6mol／L）、渥曼青霉素（10^-8mol／L）和PF-04691502（10^-6mol／L）可以减弱OrexinA的作用。结论INS-1细胞内OrexinA通过OrexinA-OXlR的介导而活化AKT信号通路，促进细胞增殖。

英文摘要：

Objective To investigate the interference effects of orexin A on cell proliferation of the insulin-secreting beta-cell line （ INS- 1 cells） through the orexin receptor 1 （OX1R） and the AKT/PKB signaling pathway. Methods INS- 1 cells were exposed to different concentrations of orexinA in vitro, and treated with OX 1R antagonist （SB334867）, PI3K antagonist （wortmannin）, or AKT antagonist （PF-04691502）. The INS- 1 cell proliferation and apoptosis, insulin secretion, OX1R protein activity and AKT phosphorylation level were determined. Results Orexin A （ 10^-10 to 10^-6 mol/L） stimulated the proliferation and activation of INS- 1 cells, prevented apoptpsis, and increased insulin secretion. Additionally, AKT phosphorylation was stimulated by orexin A （ 10^-10to 10^-6 mol/L）. The OXlR antagonist SB334867 （ 10^-6 mol/L）, the PI3K antagonist wortmannin （ 10^-6 mol/L） and the AKT antagonist PF-04691502 （ 10^-6 mol/L） weakened the effects of orexin A. Conclusion Orexin A activated the AKT sig- naling pathway through the mediation of orexin A-OX1 R, and promoted cell proliferation in INS- 1 cells.