Inceptor binds to and directs insulin towards lysosomal degradation in β cells.

ABSTRACT: Blunted first-phase insulin secretion and insulin deficiency are indicators of β cell dysfunction and diabetes manifestation. Therefore, insights into molecular mechanisms that regulate insulin homeostasis might provide entry sites to replenish insulin content and restore β cell function. Here, we identify the insulin inhibitory receptor (inceptor; encoded by the gene IIR/ELAPOR1) as an insulin-binding receptor that regulates insulin stores by lysosomal degradation. Using human induced pluripotent stem cell (SC)-derived islets, we show that IIR knockout (KO) results in enhanced SC β cell differentiation and survival. Strikingly, extended in vitro culture of IIR KO SC β cells leads to greatly increased insulin content and glucose-stimulated insulin secretion (GSIS). We find that inceptor lo

SUBMITTER: Siehler J 

PROVIDER: S-EPMC11659164 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature