Monogenic and syndromic diabetes due to endoplasmic reticulum stress

• Published in: Journal of diabetes and its complications 2021-01, Vol.35 (1), p.107618-107618, Article 107618
• Main Authors: Stone, Stephen I., Abreu, Damien, McGill, Janet B., Urano, Fumihiko
• Format: Article
• Language: English
• Subjects: Apoptosis; Atrophy; Autophagy; Congenital diseases; Diabetes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Disease; Dysphagia; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; ER stress; Etiology; Genes; Genetic medicine; Genetic testing; Hearing loss; Homeostasis; Humans; Hyperglycemia; Insulin; Insulin-Secreting Cells; Kinases; Mutation; Optic nerve; Pathogenesis; Personalized medicine; Precision medicine; Protein folding; Sleep apnea; Stress; Transcription factors; Wolfram Syndrome
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2020.107618

The endoplasmic reticulum (ER) lies at the crossroads of protein folding, calcium storage, lipid metabolism, and the regulation of autophagy and apoptosis. Accordingly, dysregulation of ER homeostasis leads to β-cell dysfunction in type 1 and type 2 diabetes that ultimately culminates in cell death. The ER is therefore an emerging target for understanding the mechanisms of diabetes mellitus that captures the complex etiologies of this multifactorial class of metabolic disorders. Our strategy for developing ER-targeted diagnostics and therapeutics is to focus on monogenic forms of diabetes related to ER dysregulation in an effort to understand the exact contribution of ER stress to β-cell death. In this manner, we can develop personalized genetic medicine for ERstress-related diabetic disorders, such as Wolfram syndrome. In this article, we describe the phenotypes and molecular pathogenesis of ERstress-related monogenic forms of diabetes. •The endoplasmic reticulum (ER) is an emerging target for understanding the mechanisms of diabetes mellitus.•Genetic forms of diabetes help us understand the exact contribution of ER stress to β-cell death.•Genetic testing helps physicians design personalized management plans for patients with genetic forms of diabetes.•Wolfram syndrome is a prototype of ERstress-associated monogenic and syndromic diabetes.