前胰高血糖素样肽-1对非糖尿病小鼠降糖作用的实验研究

摘要目的：观察胰高血糖素样肽-1（glucagon—likepeptide-1，GLP-1）的前体药物前胰高血糖素样肽-1（Pro-GLP-1）对非糖尿病小鼠的血糖和血清胰岛素水平的影响。方法：C57BL／6小鼠皮下注射不同剂量Pro-GLP-1，不同时间间隔取血测定血糖及血清胰岛素水平。结果：非糖尿病小鼠注射Pro-GLP-1后，血糖血清和胰岛素水平均无明显改变；给予糖负荷后的小鼠Pro—GLP-1呈剂量依赖性降低血糖浓度，同时升高血清胰岛素水平。等剂量Pro-GLP-1的降糖作用较GLP-1作用强。于第一次糖负荷后150min给予第二次糖负荷，Pro—GLP-1仍能发挥其降糖作用。结论：Pro—GLP-1通过葡萄糖依赖方式促进胰岛素分泌，剂量依赖性降低过高血糖，不降低正常血糖，其降糖作用可以维持3h以上。

Effects of glucagon-like peptide-1 prodrug on glycemia control in non-diabetic mice

AIM: To study the effects of proglucagon-like peptide-1,a long-acting prodrug glucagon-like peptide-1,on regulations of blood glucose levels and insulin secretion in non-diabetic mice.METHODS: Pro-GLP-1 was administered via sc route.Blood glucose levels were measured using a blood glucose meter.Plasma insulin concentrations were determined by ELISA.RESULTS: In C57BL/6 mice,native GLP-1 and Pro-GLP-1 decreased blood glucose,but Pro-GLP-1 had a more evident action.A single injection of Pro-GLP-1 dose-dependently reduced higher glucose following glucose load at least 3 h,and it had no effect on normal blood glucose.Moreover, it dose-dependently stimulated insulin secretion and significantly improved glucose tolerance after glucose challenge.CONCLUSION: These results demonstrate that Pro-GLP-1 facilitates a dose-dependently significant and prolonged glucose-lowering effect.