Type 2 diabetes is characterized by insulin resistance and pancreatic β-cell failure. Insulin resistance leads to increased insulin demand, which can lead to increased proinsulin misfolding in the endoplasmic reticulum (ER). The accumulation of the misfolded proteins in the ER can cause ER stress, which can lead to pancreatic β-cell dysfunction. Cells respond to ER stress by the unfolded protein response (UPR), which increases protein folding capacity and causes degradation of misfolded proteins. Using a pancreatic β-cell model of induced misfolded proinsulin expression (proinsulin-C96Y tagged with GFP) we discovered that one of the most highly induced genes was stromal cell-derived factor 2 like 1 (SDF2L1). SDF2L1 is an ER localized soluble protein with an as yet unknown function. In this thesis I examined the potential role of SDF2L1 in pancreatic β-cells in ER stress conditions.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31464 |
| Date | 20 December 2011 |
| Creators | Tiwari, Akansha |
| Contributors | Volchuk, Allen |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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