Year: 2014
Type: dissertation
Abstract: Endoplasmic Reticulum (ER) stress and activation of the Unfolded Protein Response (UPR) has been implicated in causing pancreatic beta cell dysfunction leading to the development of Type II diabetes. Jagn1 was identified in a proteomic screen as an upregulated protein in response to ER stress caused by mutant proinsulin production. Jagn1 is an ER membrane protein with an unknown function in mammalian cells. This thesis examined the role of Jagn1 in pancreatic beta cells. Jagn1 mRNA was detected in insulinoma cell lines and rodent islets and its levels were increased in response to ER stress. Knock-down of Jagn1 in INS-1 832/13 insulinoma cells resulted in an increase in insulin secretion, proinsulin biosynthesis and ER content compared to control cells. Conversely, overexpression of myc-Jagn1 decreased insulin protein levels, whereas overexpression of mutant Jagn1 had no effect. Overall, these results suggest that Jagn1 may regulate insulin biosynthesis in pancreatic beta cells undergoing ER stress.
Source: TSpace (University of Toronto)
Author: Courtney Nosak
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2980709459