Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells.

Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. Research Abstract Details 

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Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. Abstract Text:

Afshin Shameli,Jun Yamanouchi,Shari Thiessen,Pere Santamaria,

The high rate of protein synthesis in beta-cells renders them susceptible to endoplasmic reticulum (ER) stress, a condition that can be aggravated by additional imbalances in ER homeostasis and could potentially contribute to the pathogenesis of type-1 and type-2 diabetes. Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an ER-resident protein that is specifically expressed in pancreatic beta-cells and is a major target of diabetogenic CD8(+) T cell responses in non-obese diabetic (NOD) mice. We produced transgenic mice expressing human IGRP (hIGRP) under the control of rat insulin promoter (RIP) to study epitopes in hIGRP capable of driving diabetogenic human leukocyte antigen (HLA)-restricted CD8(+) T-cell responses in hIGRP/HLA transgenic NOD mice. Surprisingly, we found that 3 out of 14 lines expressing RIP-hIGRP in a non-T1D-prone genetic background developed a form of early-onset diabetes that was dissociated from autoimmune inflammation of pancreatic islets. We show that diabetes in these 3 lines resulted from increased rates of beta-cell death because of ER stress. We hypothesize that IGRP compounds the viability of beta-cells undergoing ER stress by generating unfolded proteins in the ER lumen, and that IGRP's location in the ER accounts, in part, for its exquisite immunogenicity in T1D-prone genetic backgrounds.

Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. Publishing Authors By Initials

A Shameli,J Yamanouchi,S Thiessen,P Santamaria,

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Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The review of diabetic studies : RDS

VOLUME: 4

Page Numbers: 25-32

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ISSN: 1614-0575

DAY: 10

MONTH: 05

YEAR: 2007

Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. Information

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LANGUAGE: eng

NlmUniqueID: 101227575

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Grant and Affiliation Information for Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells.

AFFILIATION: Julia McFarlane Diabetes Research Centre (JMDRC), Department of Microbiology and Infectious Diseases, and Institute of Infection, Inflammation and Immunity, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada T2N 4N1.

Country: Germany

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MEDLINETA: Rev Diabet Stud

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