Pelon Lin
Research Mentor: Rachel Reinert
Mentor Department: Internal Medicine/MEND, Medicine
Author(s): Pelon Lin, Rachel Reinert
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 40
Abstract
Pancreatic islet aand ß cells secrete the key metabolic hormones glucagon and insulin, respectively, which maintain blood glucose homeostasis. Insulin is secreted when blood glucose levels are high (hyperglycemia), and glucagon is secreted when blood glucose levels are low (hypoglycemia). Disrupted secretion of these hormones contributes to abnormal blood glucose levels in diabetes. Due to the high secretory demands placed on these cells, endoplasmic reticulum (ER) homeostasis is essential for maintaining their function. One critical mechanism involved in this process is SEL1L–HRD1 ER-associated degradation (ERAD), which removes misfolded proteins from the ER. We previously discovered that mice with SEL1L-ERAD deletion in their ß cells (ßKO mice) develop progressive diabetes due to decreased insulin secretion and ß cell dedifferentiation. Similarly, mice with SEL1L-ERAD deletion in their a cells (aKO mice) have decreased glucagon secretion during hypoglycemia. To better understand the role of a cells in islet dysfunction in diabetes, we developed mice with inactivation of SEL1L-HRD1 ERAD in both a and ß cells (aßKO mice). We hypothesized that these mice will still develop diabetes, but possibly with delayed onset or a lesser degree of hyperglycemia given a relative glucagon deficiency. To investigate our hypothesis, we measured random blood glucose levels with age and tested blood glucose excursions after administration of Ensure nutritional supplement. We also collected pancreas samples to measure hormone content and evaluate islet histology. These data will provide insights into a-to-ß cell communication in diabetes.
