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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.

the journal of clinical endocrinology and metabolism/journal of clinical endocrinology and metabolism

Enhanced Signaling Downstream of Ribonucleic Acid-Activated Protein Kinase-Like Endoplasmic Reticulum Kinase Potentiates Lipotoxic Endoplasmic Reticulum Stress in Human Islets