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

Abstract

Store-operated Ca2+ entry replenishes endoplasmic reticulum (ER) Ca2+ through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). β-Cell-specific deletion of STIM1 results in a sexually dimorphic phenotype, with β-cell dysfunction and loss of identity in female but not male mice. Expression of the noncanonical 17-β estradiol receptor (GPER1) is decreased in islets of female STIM1Δβ mice, and modulation of GPER1 levels leads to alterations in expression of β-cell maturity genes in INS-1 cells.