MiR-7, miR-9 and miR-375 contribute to effect of Exendin-4 on pancreatic β-cells in high-fat-diet-fed mice.

PURPOSE: The purpose of this study was to test whether glucagon-like peptide-1 (GLP-1) receptor activation preserved pancreatic β-cells via the regulation of microRNAs and target genes in high-fat-diet-fed mice.

METHODS: C57BL/6 male mice were simultaneously treated with high-fat-diet (HFD) and GLP-1 analogue, Exendin-4 (Ex-4) (3 μg/kg/day or 30 μg/kg/day), i.p. or vehicle, for consecutive 13 weeks. Fasting blood glucose, postprandial blood glucose, ΔI30/ΔG30, HOMA-IR and HOMA-% β were measured in each group. Pancreatic β-cell mass was assessed by immunohistochemistry. The expression of miRNAs and related downstream genes were investigated using quantitative real-time PCR.

RESULTS: Thirteen weeks of Ex-4 treatment significantly reduced body weight and food intake in HFD-fed mice (P.