Silencing the G-protein coupled receptor 3-salt inducible kinase 2 pathway promotes human β cell proliferation.

ABSTRACT: Loss of pancreatic β cells is the hallmark of type 1 diabetes, for which provision of insulin is the standard of care. While regenerative and stem cell therapies hold the promise of generating single-source or host-matched tissue to obviate immune-mediated complications, these will still require surgical intervention and immunosuppression. Here we report the development of a high-throughput RNAi screening approach to identify upstream pathways that regulate adult human β cell quiescence and demonstrate in a screen of the GPCRome that silencing G-protein coupled receptor 3 (GPR3) leads to human pancreatic β cell proliferation. Loss of GPR3 leads to activation of Salt Inducible Kinase 2 (SIK2), which is necessary and sufficient to drive cell cycle entry, increase β cell mass, and enhance ins

SUBMITTER: Iorio C 

PROVIDER: S-EPMC8302759 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature