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The Role of Endoplasmic Reticulum Stress in Nonimmune Diabetes: NOD.k iHEL, a Novel Model of β Cell Death
Author(s) -
SOCHA L.,
SILVA D.,
LESAGE S.,
GOODNOW C.,
PETROVSKY N.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1288.022
Subject(s) - endoplasmic reticulum , nod , unfolded protein response , nod mice , apoptosis , diabetes mellitus , programmed cell death , beta cell , genetically modified mouse , microbiology and biotechnology , endocrinology , transgene , medicine , biology , cancer research , islet , gene , biochemistry
A bstract : The final common pathway in diabetes development is β cell apoptosis. We herein describe a novel diabetes model based on transgenic NOD.k iHEL mice, wherein male mice develop diabetes due to nonimmune‐mediated β cell death. Histology and electron microscopy confirm endoplasmic reticulum (ER) abnormalities that are consistent with endoplasmic stress caused by the HEL transgene. The NOD.k iHEL model may be particularly useful for studying mechanisms of β cell death secondary to ER stress and also for testing potential therapies designed to protect β cells from stress‐induced apoptosis. The observation that only male NOD.k iHEL mice develop diabetes and exhibit ER abnormalities is intriguing and suggests these mice may be useful in deciphering the link between hyperandrogenism, insulin resistance, and diabetes.