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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。
OBJECTIVE: To observe the effect of metformin on insulin secretion in isolated rat islet cells after chronic exposure to high glucose and free fatty acids. Methods: Rat isolated islet cells were cultured in 5.5-16.7 mmol / L glucose or 5.5 mmol / L palmitate for 48 h, and then cultured with different concentrations of metformin (0-5 mg / L) for 24 h. The islet cells of each group were collected and stimulated with 5.5 ~ 16.7 mmol / L glucose for 1 h. Culture media were collected and the basal and glucose-stimulated insulin secretion (GSIS) levels determined by radioimmunoassay. Results: There was no significant difference in basal β cells and glucose stimulated insulin secretion between low glucose group (5.5 mmol / L glucose) and different concentrations of metformin (0 ~ 5 mg / L) (P> 0.05) (P <0.01). The GSIS was significantly lower than that of the control group (P <0.01). With 2.5 ~ 5 mg / L glucose (P <0.01) L Metformin intervention, β-cell basal insulin secretion in high glucose and high fat group was significantly lower than that in untreated group (P <0.01), and GSIS was significantly higher than that in untreated group (P <0.01). CONCLUSION: Metformin has no effect on the insulin secretion of β-cell in low-sugar environment. The insulin secretion of β-cell is impaired by chronic hyperglycemia and hyperglycemia. Metformin of 2.5-5 mg / L can improve the β-cell Insulin secretion dysfunction. Tip metformin hypoglycemic effect in addition to its peripheral role, the glycolysis may have β-cell direct protective effect.