Glucagon-like peptide-1 effects lipotoxic oxidative stress by regulating the expression of microRNAs.

Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 μg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 μg/kg, 100 mM, mice and INS-1 respectively) as well. Subsequently, the analysis showed that inhibited expression of miR-33 and miR-370 upregulated the expression of CPT1A and SIRT1, reversely mimics. These results demonstrated for the first time that GLP-1 improve lipotoxic oxidative stress of pancreas by regulate expression of microRNAs.

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