【摘要】 目的:观察二甲双胍对慢性暴露于高糖和高游离脂肪酸的大鼠离体胰岛细胞胰岛素分泌功能的影响。方法:将大鼠离体胰岛细胞培养于5.5~16.7 mmol/L葡萄糖或5.5 mmol/L软脂酸中48 h,再加入不同浓度二甲双胍(0~5 mg/L)培养24 h。收集各组胰岛细胞,加入5.5~16.7 mmol/L葡萄糖刺激培养1 h。收集培养液,用放免法测定其基础及葡萄糖刺激的胰岛素分泌(GSIS)水平。结果:低糖组(5.5 mmol/L葡萄糖)用不同浓度二甲双胍(0~5 mg/L)处理后的β细胞基础及葡萄糖刺激的胰岛素分泌无显著性差异(P>0.05);高糖(16.7 mmol/L葡萄糖)及高脂(0.5 mmol/L棕榈酸)组β细胞基础胰岛素分泌较对照组明显增高(P<0.01),GSIS较对照组明显降低(P<0.01);用2.5~5 mg/L二甲双胍干预后,高糖及高脂组β细胞基础胰岛素分泌较未治疗组明显降低(P<0.01),GSIS较未治疗组明显增高(P<0.01)。结论:低糖环境下,二甲双胍对β细胞胰岛素分泌功能无明显影响;慢性高糖及高脂可致β细胞胰岛素分泌功能受损;而2.5~5 mg/L二甲双胍能改善糖脂毒性所致β细胞胰岛素分泌功能异常。提示二甲双胍降糖效果除了其外周作用外,可能对糖脂中毒的β细胞具有直接保护作用。更多还原

【Abstract】 Objective: To test the effect of metformin(MF) on improving β cell insulin secretion function impaired by its chronic exposure to high concentrations of free fatty acids(FFA) or glucose.Methods: Pancreatic islets of male Wistar rats were incubated for 48 h in a medium containing 5.5-16.7 mmol/L glucose and 0.5 mmol/L palmitic acid respectively.The cells were re-incubated for another 24 h with 0-5 mg/L MF.Basal and stimulated(16.7 mmol/L glucose) insulin contents in the medium were measured by radioimmunoassay.Results: Metformin(0-5 mg/L) did not affect basal and glucose-induced insulin release in 5.5 mmol/L glucose(control).The islets exposed to high glucose or high FFA concentration showed an increased basal(P<0.01) and a decreased glucose-indused insulin release(P<0.01) as compared with control islets.However,when these islets pretreated with high glucose or high FFA re-cultured for additional 24 h in the presence of 2.5-5 mg/L MF,both basal and glucose-induced insulin secretion were reversed dosely to the control levels(P<0.01).Conclusion: Metformin do not affect β cell insulin release in 5.5 mmol/L glucose,but it is able to restore substantially the secretory function of rat pancreatic islets whose secretory function has been impaired by chronic exposure to elevated glucose or FFA levels.These data raise the possibility that metformin may have a direct beneficial effect on the β-cell secretory function.更多还原