Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance by promoting insulin biogenesis and minimizing beta cell apoptosis [ChIP-Seq]

Aims/ hypothesis: p21 (Cdc42/Rac1) activated Kinase 1 (PAK1) is depleted in type 2 diabetic human islets compared to non-diabetic (ND) human islets, and acute PAK1 restoration to type 2 diabetic human islets can restore insulin secretory function ex vivo. We hypothesized that beta cell specific PAK1 enrichment in vivo carries the capacity to mitigate high-fat diet-induced glucose intolerance by increasing the functional beta cell mass. Methods: Type 2 diabetic or ND human islets expressing exogenous PAK1 specifically in beta cells were used for bulk RNA-sequencing (RNA-seq). Human EndoC- Human EndoC-H1 cells overexpressing myc-tagged PAK1 were used for chromatin immunoprecipitation (ChIP) and ChIP-sequencing (ChIP-seq).