GLP-1类似物的葡萄糖浓度依赖性降糖机制研究

Mechanism of GLP-1 analogue on glucose-dependent hypoglycemic effect

目的探讨胰高糖素样肽-1(GLP-1)类似物(Exendin-4)对MIN6细胞的葡萄糖浓度依赖性降糖作用机制。方法检测GLP-1类似物(Exendin-4)在不同葡萄糖浓度下对体外培养的MIN6细胞的ATP水平、cAMP含量、腺苷酸环化酶活性和胰岛素分泌量的变化。结果在2.8 mmol/L葡萄糖培养条件下,Ex-endin-4使细胞三磷酸腺苷(ATP)水平无明显变化,环磷酸腺苷(cAMP)含量、腺苷酸环化酶活性和胰岛素分泌量无明显增加(P>0.05);在25 mmol/L葡萄糖培养条件下,Exendin-4使细胞ATP水平明显降低,cAMP含量、腺苷酸环化酶活性和胰岛素分泌量明显增加(P<0.05)。结论 GLP-1类似物(Exendin-4)具有葡萄糖浓度依赖的促胰岛素分泌作用,细胞内cAMP含量增加是其引起胰岛素释放的关键环节。

Objective】To explore the glucose-dependent hypoglycemic mechanism by which glucagon-like peptide-1（GLP-1） analogue stimulates insulin secretion in MIN6 cells.【Methods】We detected cAMP content,ATP level and the amount of insulin secretion in cultured MIN6 cells which were incubated with GLP-1 analogue（Exendin-4） in different glucose concentration.【Results】In the presence of 2.8 mmol/L glucose,exendin-4 could not increase cAMP content and insulin secretion in cells,and ATP level showed insignificant change（P〈 0.05）.In the presence of 25 mmol/L glucose,exendin-4 produced marked increase of insulin secretion and cAMP content,together with decreased ATP level（P〈 0.05）.【Conclusion】Exendin-4 stimulates the glucose-dependent production of cAMP.Elevated cAMP in β cells plays the key role in inducing insulin secretion.