Emily Kuruvilla
Research Mentor: Noah Gleason
Mentor Department: Int.Med Endocrinology and Diabetes, Medicine
Author(s): Emily Kuruvilla, Noah Gleason, Peter Arvan
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 130
Abstract
Diabetes mellitus is a chronic disease characterized by persistent abnormalities in blood glucose levels and impaired insulin production or secretion, affecting an estimated 40.1 million Americans annually or roughly 1 in 10 individuals. Recently, Type 5 diabetes has been recognized as a distinct form of diabetes associated with childhood or prolonged undernutrition resulting in severe insulin deficiency. Pancreatic ß-cell proinsulin synthesis is thought to be regulated by environmental nutrient availability; however, the specific nutrients and signaling mechanisms required to facilitate this process remain largely underexplored. This study aims to determine if (and if so, which) nutritional conditions support or inhibit proinsulin synthesis in pancreatic ß-cells under metabolic stress conditions. We hypothesized that incubation of pancreatic ß-cells under glucose-only or amino acid-only conditions would suppress proinsulin synthesis and activate markers of translational inhibition. Proinsulin synthesis was assessed using an SDS-PAGE/immunoblotting protocol on clonal ß-cell lines to quantify relative proinsulin abundance in cell lysate and media after incubating cells in amino acid-restricted, glucose-restricted, or complete media. Preliminary data indicate that incubating cells in complete media supports high proinsulin response and low eIF2a phosphorylation, whereas treatment with glucose alone or amino acids alone results in low proinsulin response and elevated eIF2a phosphorylation, suggesting a synergistic relationship between the two. These findings expand upon the current understanding of insulin signaling pathways by demonstrating that glucose alone is not sufficient for stimulating proinsulin synthesis. Further research is needed to determine and isolate which specific amino acids are necessary for supporting nutrient-sensitive insulin signaling pathways and is the focus of this project moving forward.
