Annissa Sisson
Pronouns: she/hers
Research Mentor(s): Rachel Reinert
Research Mentor School/College/Department: Internal Medicine/MEND / Medicine
Program: UROPF
Session: Session 5 (2:40pm – 3:30pm)
Authors: Annissa Sisson, Rachel Reinert
Abstract
A central feature of diabetes pathogenesis is dysregulated secretion of insulin and glucagon from ß and a cells of the pancreatic islets. Despite their shared importance in controlling glucose homeostasis, our understanding of a cell biology lags behind that of ß cells, and the mechanisms regulating a cell protein synthesis remain poorly understood. Secretory cells rely on quality control systems within the endoplasmic reticulum (ER) to maintain ER homeostasis and protein synthesis. Recently, we found that Sel1L-Hrd1 ER-associated degradation (ERAD), a substrate-specific mechanism for clearing misfolded or excessive ER proteins, is critical for maintenance of islet a cell glucagon production and survival. ERAD deficiency also leads to reduced expression of transthyretin, one of the most abundant proteins in a cells whose function in islet physiology remains unclear. In this project, we explored the relationship between transthyretin and glucagon expression in islet a cells in ERAD deficiency and in mouse models of insulin resistance and/or diabetes. This work advances our understanding of the potential roles for transthyretin in islet a cell function.
