GLP-1 receptor agonist protects glucose-stimulated insulin secretion in pancreatic β-cells against lipotoxicity via PPARδ/UCP2 pathway.

ABSTRACT: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) enhance glucose-stimulated insulin secretion (GSIS). Peroxisome proliferator-activated receptor δ (PPARδ) plays an essential role in mitochondrial function and glucose homeostasis. This study investigated the role of PPARδ in the protective effects of GLP-1RAs on pancreatic β-cells against lipotoxicity. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were treated with exenatide (Exe), GW501516 (GW, a PPARδ agonist), saline, or dimethyl sulfoxide (DM) for 8 weeks, followed by phenotypic assessments. In vitro, mouse pancreatic β-cells (NIT-1 cells) were exposed to palmitic acid (PA), PA + exendin-4 (Ex-4), PA + GW, PA + GSK0660 (GSK, a PPARδ antagonist), or PA + Ex-4 + GSK. Compared to HFD mice treated with saline or DM, Exe and GW ad

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12575910 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature