Riyah Alnsour
Pronouns: she/her
Research Mentor(s): Sivakumar Jeyarajan
Research Mentor School/College/Department: Pharmacology / Medicine
Program:
Authors:
Session: Session 3: 11:00 am – 11: 50 am
Poster: 40
Abstract
The present study analyzes insulin secreting cells and the impact of different molecular mechanisms in mediating insulin secretion. The purpose of this project is to understand the role of calcium and ATP energetics in insulin secreting cells to fill in the gaps of previously discovered mechanisms. In Pancreatic Beta-cells, the Endoplasmic Reticulum (ER) is responsible for insulin folding and transportation for exocytosis. In Type II Diabetes, the ER is under stress, and these conditions cause fluctuations in the ATP and calcium levels causing insulin misfolding and alters insulin pulsation. Insulin folding requires both ATP and calcium to be properly synthesized and folded. The ER transports calcium through SLC35B1/AXER and can also get calcium through other mitochondrial associated membranes (MAMs). In previous studies, high levels of calcium located in the cytosol has shown to inhibit movement of ATP into the ER via the SLC35B1/AXER channel. However, under conditions of stress the ER necessitates the import of ATP for use. ATP has been shown to inhibit calcium transportation into the ER. To study this, a plasmid containing a fluorescent probe was transfected into cells to measure ATP and ER calcium simultaneously in an intracellular system.The cell are treated during imaging with cyclopiazonic acid (CPA), an inhibitor that blocks transportation into the ER via the SERCA pump, and Azide an inhibitor of oxidative phosphorylation which inhibits formation of ATP. This is in order to determine the response when ER is stressed which increases cytosolic calcium and inhibits ATP, but also the function that occurs when the ER is stressed and requires ATP movement into the ER. The conflicting nature of these two responses is being studied in order to determine maintenance functions of the ER. The movement of ATP and calcium and their fluctuating levels are imaged using the probe and provide measurements during normal and stressed ER conditions.
