Endoplasmic reticulum stress, pancreatic β-cell degeneration, and diabetes

• Published in: Cold Spring Harbor perspectives in medicine Vol. 2; no. 9; p. a007666
• Main Author: Papa, Feroz R
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.09.2012
• Subjects: Apoptosis; Cell Death - genetics; Diabetes Mellitus - drug therapy; Diabetes Mellitus - genetics; Diabetes Mellitus - pathology; Endoplasmic Reticulum Stress - genetics; Endoplasmic Reticulum Stress - physiology; Humans; Insulin-Secreting Cells - physiology; Mutation - genetics; Signal Transduction - physiology; Unfolded Protein Response - genetics; Unfolded Protein Response - physiology
• ISSN: 2472-5412
• DOI: 10.1101/cshperspect.a007666

Overwhelming of protein folding in the endoplasmic reticulum (ER)--referred to as "ER stress"--activates a set of intracellular signaling pathways termed the unfolded protein response (UPR). Beneficial outputs of the UPR promote adaptation in cells experiencing manageably low levels of ER stress. However, if ER stress reaches critically high levels, the UPR uses destructive outputs to trigger programmed cell death. Genetic mutations in various UPR components cause inherited syndromes of diabetes mellitus in both rodents and humans, implicating the UPR in the proper functioning and survival of pancreatic islet β cells. Markers of chronically elevated ER stress, terminal UPR signaling, and apoptosis are evident in β cells in these rare disorders; these markers are similarly present in islets of human patients with common forms of diabetes. These findings promise to enhance our molecular understanding of human diabetes significantly and may lead to new and effective therapies.