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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18337

Title: Endoplasmic Reticulum Stress in Pancreatic Beta-cells
Authors: Hartley, Taila
Advisor: Volchuk, Allen
Department: Biochemistry
Keywords: Endoplasmic Reticulum Stress
Beta Cells
Issue Date: 25-Jan-2010
Abstract: Endoplasmic reticulum (ER) stress has been implicated in pancreatic beta-cell loss contributing to diabetes mellitus, however the molecular mechanisms of ER stress-induced apoptosis are unclear. In the first project of this thesis, the contribution of ER stress in proinflammatory cytokine-mediated beta-cell dysfunction and apoptosis is examined. Although exogenous cytokine treatment did induce unfolded protein response (UPR) genes, increased chaperone capacity had no effect on apoptosis induction, insulin biosynthesis and insulin secretion. Thus, ER stress is most likely not an important pathway in cytokine toxicity under our experimental system. The second project develops a pathophysiological model of ER stress based on the mutant misfolded insulin of the Akita mouse. Microarray analysis was conducted and we observed early induction of ER chaperone and ER-associated degradation (ERAD) genes, followed by a large increase in pro-apoptotic genes with mutant insulin expression. A detailed analysis of the ER stress response in this system is presented.
URI: http://hdl.handle.net/1807/18337
Appears in Collections:Master
Department of Biochemistry - Master theses

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