BME PhD Preliminary Exam Announcement for Madeline McLaughlin (C. Evans-Molina and F. Huang, co-advisors)

Everyone is invited to attend the public presentation beginning at 2:00 pm.

Research Title: STIM1 Interacts with G Protein-Coupled Estrogen Receptor Signaling to Maintain Beta Cell Identity in Female Mice 

Date: March 18, 2024 

Time: 2:00 pm

Place: Zoom - https://iu.zoom.us/j/8318926012

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) is a global health pandemic resulting from a combination of defective insulin secretion and impaired insulin action in peripheral tissues; however, genetic and physiologic data suggest that inadequate insulin secretion from the b cell is the chief determinant predicting T2D development. Studies have identified b cell dedifferentiation as one potential mechanism leading to b cell failure. During dedifferentiation, b cells lose expression of key identity markers and insulin secretory function and may differentiate into other endocrine cell types.  At present, the molecular mechanisms leading to b cell dedifferentiation are not well understood. Calcium (Ca²⁺) plays a vital role in regulating b cell health and function, and the endoplasmic reticulum (ER) serves as the dominant Ca²⁺ store. ER Ca²⁺ depletion triggers the rescue mechanism store-operated Ca²⁺ entry (SOCE) which replenishes ER Ca²⁺ stores through the ER-localized Ca²⁺ sensor stromal interaction molecule 1 (STIM1). Our laboratory recently found that obese female mice with reduced SOCE due to b cell-specific genetic deletion of STIM1 had evidence of b cell dedifferentiation and reduced G protein coupled estrogen receptor (GPER) expression, suggesting an interaction between SOCE, GPER signaling, and b cell identity. Therefore, we hypothesize that decreased SOCE leads to reduced GPER signaling and loss of b cell identity and function, thereby contributing to the pathophysiology of T2D in females. We propose using an ovariectomy mouse model and novel imaging methods to test this hypothesis and identify a novel mechanism linking SOCE and GPER signaling to b cell failure during T2D.