国产重组人胰升血糖素样肽-1(7-36)联合西格列汀对糖尿病比格犬血糖的影响

Effect of recombination human GLP-1(7-36) combined with Sitagliptin on plasma glucose in diabetic beagle dogs

目的观察国产重组人胰升血糖素样肽—1(rhGLP-1)联合西格列汀对糖尿病犬降糖效果。方法对T2DM犬予单次rhGLP-1(G组)、西格列汀(S组)或rhGLP—1联合西格列汀(GS组)及连续2周rhGLP-1联合西格列汀治疗(2wGS组);与对照(Ctr组)比较,观察其OGTT后血糖、血GLP-1、胰岛素、胰升血糖素水平的变化。结果与Ctr对照组比较,G、S和GS组血糖下降不明显。2wGS治疗组OGTT血糖曲线下面积(AUC)降低(2710.1 vs 1238.4 min·mmol/L,P<0.05);血GLP-1浓度在30min(14.9vs125.4 pmol/L)、60 min(18.9vs359.7 pmol/L)和120 min(8.7 vs 88.7 pmol/L)均升高(P<0.05);糖负荷后30 min胰岛素分泌峰值升高(2.39 vs9.87μU/ml,P<0.05)、血胰升血糖素降低(10.60vs3.79 ng/ml,P<0.05)。结论国产rhGLP—1联合西格列汀治疗两周,能增加胰岛素分泌、抑制胰升血糖素分泌,使血糖水平降低。

Objective To examine the anti-hyperglycemic effect of rhGLP-1 combined with sitagliptin in diabetic beagle dogs.Methods Diabetic beagle dogs were divided into five groups：rhGLP-1（G group）,Sitagliptin（S group）,rhGLP-1 plus Sitagliptin（GS group）,2-week rhGLP-1 plus Sitagliptin（2wGS group） and control（Ctr group） respectively.Plasma glucose,GLP-1,insulin and glucagon during the oral glucose tolerance test（OGTT） were measured at baseline and after treatment.Results Decrease of plasma glucose was not significant in G,S GS groups as compared with Ctr group.AUC of plasma glucose reduced significantly in 2wGS group（2710.1 vs 1238.4 min ？ mmol/L,P-0.05）.The GLP-1 level at 30 min（14.9 vs 125.4 pmol/L）,60 min（18.9 vs 359.7 pmol/L）,and 120 min（8.7 vs88.7 pmol/L） were significantly increased（P〈0.05）.The peak of insulin at OGTT 30 min increased（2.39 vs 9.87 μU/ml,P〈0.05）,while glucagon decreased（10.60 vs 3.79 ng/ml,P 0.05）.Conclusion Treatment of rhGLP-1 combined with sitaliptin for two weeks significantly increased insulin secretion,inhibitd glucagon secretion thus decreased plasma glucose.