NF-κB在甘精胰岛素拮抗胰岛β细胞脂性凋亡中的作用

目的探讨①核因子κB(NF-κB)在游离脂肪酸(FFA)诱导的胰岛β细胞凋亡中的作用;②观察甘精胰岛素(glargine)对FFA诱导的胰岛β细胞凋亡的拮抗作用是否与NF-κB有关。方法Western blot检测FFA对RIN-m细胞NF-κB活性的影响,以及glargine或普通胰岛素(RI)和FFA共同孵育细胞对NF-κB活性的影响;流式细胞仪测定NF-κB抑制剂Bay-117082对FFA诱导的RIN-m细胞凋亡的影响,以及Bay-117082对glargine和RI的抗凋亡作用的影响。结果NF-κB活性在FFA孵育后增加,抑制NF-κB活性使FFA诱导的凋亡增加;glargine和RI增加FFA所导致的NF-κB激活,抑制NF-κB活性能阻断glargine及RI的抗凋亡作用。结论NF-κB在FFA诱导胰岛β细胞凋亡时被激活,NF-κB激活对FFA诱导的凋亡可能起拮抗作用;glargine和RI的抗凋亡作用可能通过NF-κB途径。

Role of NF-κB in the cytoprotective effects of glargine on free fatty acid-induced pancreatic β cell apoptosis

Aim① To investigate the role of NF-κB in free fatty acid(FFA)-induced pancreatic β cell apoptosis ② To elucidate the NF-κB activity in the cytoprotective effects of glargine on free fatty acid-treated pancreatic β cells.Methods Apoptosis was characterized by morphological analysis with invert microscope as well as Hoechst 33342 staining under a fluorescence microscope.Effects of FFA incubation on NF-κB activity in RIN-m cells as well as influence of co-incubation with FFA and glargine or regular insulin(RI) on NF-κB activity were determined by Western blot.Impacts of Bay-117082,which is specific NF-κB inhibitor on apoptosis induced by FFA and the anti-apoptotic effects of glargine and RI were measured by cytometry.Results NF-κB activity was elevated with FFA-treatment and suppression of NF-κB activity increased apoptosis induced by FFA.Co-incubation with FFA and glargine or RI caused more potent increase in NF-κB activity than FFA incubation.Suppression of NF-κB activity abolished the cytoprotective effects of glargine and RI.Conclusion Our data suggest NF-κB activation during the apoptosis of pancreatic β cell induced by free fatty acid and an anti-apoptotic role of NF-κB.To our knowledge,we report the first time that the cytoprotective effects of glargine and regular insulin are mediated via NF-κB pathway.