ArticleLaboratory investigation; a journal of technical methods and pathology2020
Wolfram syndrome 1 gene regulates pathways maintaining beta-cell health and survival.
Article in Laboratory investigation; a journal of technical methods and pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The Impact of Mutations in Wolframin on Psychiatric Disorders.Frontiers in pediatrics · 2021Pooled it
- A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.JCI insight · 2021Trial
- Genetic Variants Associated with Response to GLP-1 Receptor Agonists in Diabetes and Obesity.Life (Basel, Switzerland) · 2026Review
- Deletion ofBiology · 2026Article
- The Genetic Landscape and Precision Medicine in Neonatal Diabetes Mellitus: From Molecular Mechanisms to Clinical Management.Current issues in molecular biology · 2026Review
- The integrated stress response in pancreatic β-cell failure in diabetes: from molecular mechanisms to precision therapeutics.Frontiers in endocrinology · 2026Review
- Article
- A Compound Screen Based on Isogenic hESC-Derived β Cell Reveals an Inhibitor Targeting ZnT8-Mediated Zinc Transportation to Protect Pancreatic β Cell from Stress-Induced Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Topology ofPediatric diabetes · 2025Article
- A WFS1 variant disrupting acceptor splice site uncovers the impact of alternative splicing on beta cell apoptosis in a patient with Wolfram syndrome.Diabetologia · 2025Article
- Diabetes mellitus and pregnancy in Wolfram syndrome type 1: a case report with review of clinical and pathophysiological aspects.Frontiers in medicine · 2025Article
- RNASeq highlights ATF6 pathway regulators for CHO cell engineering with different impacts of ATF6β and WFS1 knockdown on fed-batch production of IgGScientific reports · 2024Article
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Review
- ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models.Cell death and differentiation · 2024Article
- Investigation of Monogenic Diabetes Genes in Thai Children with Autoantibody Negative Diabetes Requiring Insulin.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Genotype and Clinical Characteristics of Patients with Wolfram Syndrome and WFS1-related Disorders.medRxiv : the preprint server for health sciences · 2023Article
- Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders.Frontiers in genetics · 2023Article
- Novel Mutations of PAX6 and WFS1 Associated With Congenital Cataract in a Chinese Family.Cureus · 2023Article
- Paediatric Wolfram syndrome Type 1: should gonadal dysfunction be part of the diagnostic criteria?Frontiers in endocrinology · 2023Article
- The Role of ER Stress in Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Wolfram Syndrome 1 (WFS1) protein is an endoplasmic reticulum (ER) factor whose deficiency results in juvenile-onset diabetes secondary to cellular dysfunction and apoptosis. The mechanisms guiding β-cell outcomes secondary to WFS1 function, however, remain unclear. Here, we show that WFS1 preserves normal β-cell physiology by promoting insulin biosynthesis and negatively regulating ER stress. Depletion of Wfs1 in vivo and in vitro causes functional defects in glucose-stimulated insulin secretion and insulin content, triggering Chop-mediated apoptotic pathways. Genetic proof of concept studies coupled with RNA-seq reveal that increasing WFS1 confers a functional and a survival advantage to β-cells under ER stress by increasing insulin gene expression and downregulating the Chop-Trib3 axis, thereby activating Akt pathways. Remarkably, WFS1 and INS levels are reduced in type-2 diabetic (T2DM) islets, suggesting that WFS1 may contribute to T2DM β-cell pathology. Taken together, this work reveals essential pathways regulated by WFS1 to control β-cell survival and function primarily through preservation of ER homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.