GPRC5B preserves a mature β cell state in obesity by controlling MafA expression.

ABSTRACT: In vitro studies have implicated orphan receptor GPRC5B in β cell survival, proliferation, and insulin secretion, but its relevance for glucose homeostasis in vivo is largely unknown. Using tamoxifen-inducible, β cell-specific GPRC5B-KO mice (Ins-G5b-KOs), we show here that loss of GPRC5B does not affect β cell function in the lean state but results in strongly reduced insulin secretion and disturbed glucose tolerance in mice subjected to high-fat diet for 16 weeks. Flow cytometry and single-cell expression analyses in islets from obese mice show a reduced β cell abundance and a less mature β cell phenotype in Ins-G5b-KOs. Expression of β cell-specific transcription factor MafA is reduced both on the RNA and protein level, as are transcripts of MafA target genes. Mechanistically, we show t

SUBMITTER: Wang T 

PROVIDER: S-EPMC12581666 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature