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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/11149

Title: Diabetes and Endoplasmic Reticulum Stress in Pancreatic beta-cells: Effects on Insulin Biosynthesis and beta-cell Apoptosis
Authors: Lai, Elida Wing Shan
Advisor: Volchuk, Allen
Department: Biochemistry
Keywords: pancreatic beta-cells
type 2 diabetes
ER stress
apoptosis
pancreatic beta-cell dysfunction
free fatty acids
lipotoxicity
palmitate
high glucose
hyperglycemia
glucotoxicity
insulin biosynthesis
unfolded protein response
chaperone
GRP78
PDI
INS-1
MIN6
human islets
stable cell line
Issue Date: 30-Jul-2008
Abstract: Chronic hyperlipidemia (lipotoxicity) and hyperglycemia (glucotoxicity) have recently been shown to induce Endoplasmic Reticulum (ER) stress, which may contribute to pancreatic beta-cell dysfunction in type 2 diabetes. This thesis examined the involvement of ER stress in beta-cell lipotoxicity and glucotoxicity. Although chronic treatment with saturated free fatty acids (FFA) in vitro induced ER stress, altering ER stress by increasing or knocking-down GRP78 chaperone expression had no effect on apoptosis induction. Conversely, overexpression of ER chaperones rescued the reduction in proinsulin protein levels caused by chronic exposure to high glucose, although it had no effect on the decreased insulin mRNA levels and proinsulin translation rate. Thus, ER stress is likely not the main mechanism involved in saturated FFA-induced beta-cell apoptosis in vitro, but it may contribute to glucotoxic effects on proinsulin levels. These findings have increased our understanding of the link between ER stress and beta-cell dysfunction in type 2 diabetes.
URI: http://hdl.handle.net/1807/11149
Appears in Collections:Master
Department of Biochemistry - Master theses

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