Abstract:
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.
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