Andrea Herrmann
Pronouns: she/her/hers
Research Mentor(s): Irina Zhang
Co-Presenter:
Research Mentor School/College/Department: pharmacology / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 6 – 4:40pm – 5:30 pm
Room: Breakout room 6
Authors:
Presenter: 2
Abstract
Glucose homeostasis is maintained through the release of insulin from pancreatic beta-cells following the increase of plasma glucose. Insulin secretion is pulsatile, due to oscillations in the concentrations of beta-cell cytosolic Ca2+. The endoplasmic reticulum (ER) helps to regulate the cytosolic Ca2+ level, thereby playing a role in Ca2+-induced insulin release. Accumulation of unfolded proteins in the ER can bring on ER stress, which can lead to the ER Ca2+ depletion, which can contribute to beta-cell deterioration and an increased risk for Type-2 Diabetes. We sought to determine the effect of tunicamycin (TM)-induced ER stress on ER Ca2+ channels, inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs) and ryanodine receptors (RyRs), and subsequent alterations in beta-cell Ca2+ homeostasis that result from these altercations. We found that RyR1 was upregulated in response to TM through qRT-PCR. To determine the roles of these receptors in TM-induced beta-cell dysfunction, we treated mouse pancreatic islets with RyR1 inhibitor dantrolene (Dan) or the IP3R inhibitor xestospongin C (XeC) along with TM. Beta cells treated with TM exhibited altered cytosolic Ca2+ when in sub-threshold glucose compared to vehicle controls, and the oscillations were abolished by co-treatment of Dan or knocking down RyR1, but not XeC. We also found that neither Dan or XeC-treatment reversed UPR activation in insulin secreting INS-1 (832/13) cells. Taken together, these results suggest that RyR1 plays a critical role in mediating the disturbed cellular Ca2+ homeostasis seen in response to the induction of ER stress. The study reveals a potential drug target for Type-2 diabetes.
Biomedical Sciences, Interdisciplinary
