BME PhD Defense Announcement for Madeline R. McLaughlin (C. Evans-Molina and F. Huang, advisors) Everyone is invited to attend the public presentation beginning at 9:30 am. Research Title: STIM1 Interacts with G Protein-Coupled Estrogen Receptor Signaling to Maintain β Cell Identity in Female Mice Date: February 12, 2025 Time: 9:30 am Place: Zoom - https://iu.zoom.us/j/83242015222<https://nam04.safelinks.protection.outlook.com/?url=https%3A%2F%2Fiu.zoom.us%2Fj%2F83242015222&data=05%7C02%7Cbmeroundtable-list%40ecn.purdue.edu%7C93535595521a48526d3008dd408e8409%7C4130bd397c53419cb1e58758d6d63f21%7C0%7C0%7C638737703015345351%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=2vgRB8Eo7dW78pV2e8KMrp9IBMEuYsNs4NdHl6Y3pdA%3D&reserved=0> Committee Members: Dr. Carmella Evans-Molina (Co-Chair), Dr. Fang Huang (Co-Chair), Dr. Sherry Harbin, and Dr. Qing Deng Abstract: Type 2 diabetes (T2D), a multi-factorial disease characterized by insulin resistance and pancreatic β cell dysfunction, accounts for 90% of all forms of diabetes. Recent studies identified β cell dedifferentiation as one mechanism leading to β cell failure in T2D, and this phenotype has been linked with loss of expression of cellular identity markers​. The molecular mechanisms leading to β cell dedifferentiation in T2D are not well defined and represent a key gap in our understanding of disease progression. Furthermore, sex-specific mechanisms contributing to β cell dysfunction remain unknown. We demonstrated that β cell-specific STIM1 knockout (STIM1Δβ) leads to obesity-induced glucose intolerance and reduced expression of β cell identity genes in female but not male mice. Mechanistic studies identified reduced G-protein coupled estrogen receptor (GPER) expression in female STIM1Δβ islets, suggesting a novel connection between STIM1, GPER, and β cell identity. To determine how STIM1 and GPER interact to maintain β cell identity in females, we generated and characterized two mouse models: a surgical ovariectomy (OVX) model and a β cell-specific GPER knockout (GPERDβ) model. Female high fat diet (HFD)-fed OVX mice showed glucose intolerance and loss of β cell identity gene expression, and ex vivo treatment of OVX islets with a GPER agonist rescued the loss of β cell identity. Additionally, HFD-fed GPERDβ female mice had increased glucose excursions compared to controls. Our results highlight the critical role that estradiol signaling through GPER plays in the maintenance of β cell health and identity and the pathogenesis of T2D in females. -- Bmeroundtable-list mailing list Bmeroundtable-list@ecn.purdue.edu https://engineering.purdue.edu/ECN/mailman/listinfo/bmeroundtable-list