Dataset Information

Stromal Interaction Molecule 1 Maintains Beta Cell Identity and Function in Female Mice through Preservation of G Protein-Coupled Estrogen Receptor 1 Signaling

ABSTRACT: Loss of pancreatic Beta cell mass, identity, and function contribute to the development of diabetes. Here, we show that the endoplasmic reticulum (ER) calcium sensor, stromal interaction molecule 1 (STIM1), is critical for the maintenance of Beta cell function in female mice. When mice with Beta cell- specific deletion of STIM1 (STIM1-delta-Beta) were challenged with high-fat diet, Beta cell dysfunction was observed in female, but not male, mice. Impaired glucose tolerance was accompanied by reductions in Beta cell mass, a concomitant increase in alpha cell mass, and significant reductions in the expression of markers of Beta cell maturity, including MafA and UCN3. Mechanistic assays demonstrated that the sexually dimorphic phenotype observed in STIM1-Delta-Beta mice was due in part to loss of signaling through the noncanonical 17-Beta estradiol receptor, GPER1. Together, these data suggest that STIM1 orchestrates pancreatic Beta cell function and identity through GPER1- mediated estradiol signaling.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Rattus Norvegicus (ncbitaxon:10116)

SUBMITTER: Amber Mosley Carmella Evans-Molina