二甲双胍促进2型糖尿病小鼠支链氨基酸分解代谢

目的 通过观察二甲双胍（Met）对高脂联合链脲佐菌素（STZ）诱导的2型糖尿病（T2DM）小鼠支链氨基酸（BCAAs）分解代谢作用并探讨其作用机制。 方法 通过高脂饮食+注射小剂量链脲佐菌素（STZ）途径构建T2DM小鼠模型。经随机分组，将20只C57BL / 6J雄性小鼠归入下述四组:正常对照组，2型糖尿病（T2DM）组，T2DM+安慰剂（T2DM+Vehicle）组，T2DM+二甲双胍治疗（T2DM+MET）组。高效液相色谱-串联质谱法检测小鼠血浆中的BCAA水平。实时荧光定量PCR检测小鼠心脏、肝脏和骨骼肌中BCAA分解代谢相关分子mRNA水平。Western Blot方法检测限速酶支链α-酮酸脱氢酶（BCKDH）活性，即P-BCKD / BCKD的水平。 结果 与正常对照组相比，T2DM小鼠的血浆BCAA水平明显升高（P<0.05）；BCKDH酶活性显著降低（P<0.05）；BCAA分解代谢相关分子mRNA水平显著降低（P<0.05）。二甲双胍治疗的T2DM小鼠血浆BCAA含量显著降低（P<0.05），促进BCAA分解代谢的相关分子的mRNA水平显著提高（P<0.05），BCKDH活性显著提高（P<0.05）。 结论 二甲双胍治疗可纠正T2DM小鼠血浆BCAA水平，为临床治疗BCAA代谢异常相关疾病提供了新思路。

Metformin promotes the catabolism of BCAA in T2DM mice

AIM To observe the effect of metformin on branched chain amino acids (BCAA) catabolism in type 2 diabetes mellitus, and study the preliminary mechanism. METHODS A mouse model of type 2 diabetes was established by high fat diet combined with low dose streptozotocin (STZ) injection. Twenty male C57BL/6J mice were randomly divided into 4 groups: Normal control group, type 2 diabetes (T2DM) group, T2DM+placebo (T2DM+Vehicle) group, T2DM+Metformin treatment (T2DM+MET) group. Tandem High Performance Liquid Chromatography-Mass Spectrometry was adopted for detection of plasma BCAA level in mouse. Fluorescence real-time quantitative PCR was used to detect mRNA levels of BCAA catabolism related molecules in mouse heart, liver and skeletal muscle. Western Blot method was used to detect the activity of branched α-keto acid dehydrogenase complex (BCKDH) as the level of P-BCKD/BCKD. RESULTS Compared with the control group, the plasma BCAA level in T2DM mice was significantly increased (P<0.05). The BCKDH enzyme activity was decreased significantly (P<0.05). The mRNA level of BCAA catabolism related molecules was significantly decreased (P<0.05). In T2DM mice treated with metformin, plasma BCAA level was decreased significantly (P<0.05), mRNA level of relevant molecules promoting BCAA catabolism was increased significantly (P<0.05), BCKDH activity was increased significantly (P<0.05). CONCLUSION Metformin can correct plasma BCAA level in T2DM mice and provide a new idea for clinical treatment of BCAA metabolic disorder related diseases.