CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent K_ATP channel closure.

ABSTRACT: Hallmarks of mature β cells are restricted proliferation and a highly energetic secretory state. Paradoxically, cyclin-dependent kinase 2 (CDK2) is synthesized throughout adulthood, its cytosolic localization raising the likelihood of cell cycle-independent functions. In the absence of any changes in β cell mass, maturity, or proliferation, genetic deletion of Cdk2 in adult β cells enhanced insulin secretion from isolated islets and improved glucose tolerance in vivo. At the single β cell level, CDK2 restricts insulin secretion by increasing K_ATP conductance, raising the set point for membrane depolarization in response to activation of the phosphoenolpyruvate (PEP) cycle with mitochondrial fuels. In parallel with reduced β cell recruitment, CDK2 restricts oxidative glucose meta

SUBMITTER: Sdao SM 

PROVIDER: S-EPMC7882066 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature