Open AccessEnhanced Signaling Downstream of Ribonucleic Acid-Activated Protein Kinase-Like Endoplasmic Reticulum Kinase Potentiates Lipotoxic Endoplasmic Reticulum Stress in Human Islets
Author(s) -
Laurence Ladrière,
Mariana IgoilloEsteve,
Daniel A. Cunha,
JeanPierre Brion,
Marco Bugliani,
Piero Marchetti,
Décio L. Eizirik,
Miriam Cnop
Publication year - 2010
Publication title -
the journal of clinical endocrinology and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.206
H-Index - 353
eISSN - 1945-7197
pISSN - 0021-972X
DOI - 10.1210/jc.2009-2322
Subject(s) - endoplasmic reticulum , unfolded protein response , microbiology and biotechnology , medicine , endocrinology , phosphorylation , lipotoxicity , protein kinase a , protein kinase r , dephosphorylation , biology , chemistry , insulin , insulin resistance , mitogen activated protein kinase kinase , phosphatase
Free fatty acids cause pancreatic beta-cell apoptosis and may contribute to beta-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. Eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation is an adaptive response to ER stress, and reductions in eIF2alpha phosphorylation trigger beta-cell failure. Salubrinal inhibits eIF2alpha dephosphorylation and has been proposed as a novel therapy for diabetes.
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