PMID- 17565413
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20121002
LR  - 20200622
IS  - 1614-0575 (Electronic)
IS  - 1613-6071 (Print)
IS  - 1613-6071 (Linking)
VI  - 4
IP  - 1
DP  - 2007 Spring
TI  - Endoplasmic reticulum stress caused by overexpression of islet-specific 
      glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells.
PG  - 25-32
AB  - 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.
FAU - Shameli, Afshin
AU  - Shameli A
AD  - 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.
FAU - Yamanouchi, Jun
AU  - Yamanouchi J
FAU - Thiessen, Shari
AU  - Thiessen S
FAU - Santamaria, Pere
AU  - Santamaria P
LA  - eng
PT  - Journal Article
DEP - 20070510
PL  - Singapore
TA  - Rev Diabet Stud
JT  - The review of diabetic studies : RDS
JID - 101227575
PMC - PMC1892522
EDAT- 2007/06/15 09:00
MHDA- 2007/06/15 09:01
PMCR- 2008/05/10
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/06/15 09:01 [medline]
PHST- 2007/06/15 09:00 [entrez]
PHST- 2008/05/10 00:00 [pmc-release]
AID - 10.1900/RDS.2007.4.25 [doi]
PST - ppublish
SO  - Rev Diabet Stud. 2007 Spring;4(1):25-32. doi: 10.1900/RDS.2007.4.25. Epub 2007 
      May 10.