Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca²⁺-PPP3/calcineurin-TFEB axis.

ABSTRACT: Macroautophagy/autophagy is critical for the regulation of pancreatic β-cell mass and its deregulation has been implicated in the pathogenesis of type 2 diabetes (T2D). We have previously shown that treatment of pancreatic β-cells with the GLP1R (glucagon like peptide 1 receptor) agonist exendin-4 stimulates autophagic flux in a setting of chronic nutrient excess. The aim of this study was to identify the underlying pathways contributing to enhanced autophagic flux.Pancreatic β-cells (INS-1E),mouse and human islets were treated with glucolipotoxic stress (0.5 mM palmitate and 25 mM glucose) in the presence of exendin-4. Consistent with our previous work, exendin-4 stimulated autophagic flux. Using chemical inhibitors and siRNA knockdown, we identified RAPGEF4/EPAC2 (Rap guanine nucleotide

SUBMITTER: Zummo FP 

PROVIDER: S-EPMC9037459 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature