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目的：探讨5-氨基乙酰丙酸(5-ALA )对二甲双胍( Met)降血糖作用的影响及其机制。方法腹腔注射链脲菌素诱导小鼠糖尿病模型,用5-ALA和Met治疗30 d,监测小鼠体征,检测空腹血糖、葡萄糖耐量、血浆胰岛素、瘦素水平,评估胰岛素敏感性,进行肝脏、胰腺组织学检查。结果添加5-ALA的Met组比单用Met组血糖、糖耐量实验的曲线下面积均明显降低；血浆胰岛素、瘦素水平有所下降,胰岛素敏感性改善更为明显。模型组小鼠肝窦周围细胞排列紊乱,可见空泡样变；给药各组均未见此改变。模型组小鼠胰岛数量及细胞胞质较正常组明显减少,胞核固缩；添加5-ALA的各治疗组胰岛数量均较模型组增多,细胞形态趋于正常,且呈现出一定的5-ALA剂量依赖性。结论5-ALA可通过提高胰岛素敏感性及保护肝脏、胰腺的形态与功能,增强Met的降血糖作用。“,”Aim Toexaminethecombinedeffectsof 5-ALA and metformin on diabetes mellitus induced by streptozotocin( STZ) in mice, and to discuss the mech-anisminitially.Methods Thediabeticmiceinduced by intraperitoneal injection of STZ were treated with 5-ALA and/or metformin for 30 days. Physical signs, fasting blood glucose ( FBG ) , fasting plasma insulin ( FIns) , plasma leptin ( Lep) , glucose tolerance, and histological changes of liver and pancreas were as-sessed. Insulin resistance was evaluated by the homeo-stasismodelassessment(HOMA).Results There were more significant effects when 5-ALA combined with metformin than only using metformin on lowering FBG, FIns and Lep. And 5-ALA combined with met-formin could improve glucose tolerance and the insulin sensitivity. Microscopic analysis demonstrated that sig-nificant changes in pancreatic islet and characteristic feature of the vacuolization phenotype in liver was ob-served on diabetic mice, and use of 5-ALA could in-hibit shrinking pancreatic islet number and hepatic morphological changes, especially in combination with metformin.Conclusions Asynergisticeffectof5-ALA and metformin is observed. Combined therapy of 5-ALA and metformin can decrease FBG and improve glucose tolerance, insulin sensitivity and islet ? cells function and morphology.