Quantitative proteomics reveals novel interaction partners of Rac1 in pancreatic ?-cells: Evidence for increased interaction with Rac1 under hyperglycemic conditions.

ABSTRACT: Rac1, a small G protein, regulates physiological insulin secretion from the pancreatic ?-cell. Interestingly, Rac1 has also been implicated in the onset of metabolic dysfunction of the ?-cell under the duress of hyperglycemia (HG). This study is aimed at the identification of interaction partners of Rac1 in ?-cells under basal and HG conditions. Using co-immunoprecipitation and UPLC-ESI-MS/MS, we identified 324 Rac1 interaction partners in INS-1832/13?cells, which represent the largest Rac1 interactome to date. Furthermore, we identified 27 interaction partners that exhibited increased association with Rac1 in ?-cells exposed to HG. Western blotting (INS-1832/13?cells, rat islets and human islets) and co-immunoprecipitation (INS-1832/13?cells) further validated the identity of these Rac1 interaction partners including regulators of GPCR-G protein-effector coupling in the islet. These data form the basis for future investigations on contributory roles of these Rac1-specific signaling pathways in islet ?-cell function in health and diabetes.

SUBMITTER: Damacharla D 

PROVIDER: S-EPMC6686664 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature