ArticleDiabetes2011
β-cell dysfunctional ERAD/ubiquitin/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 122 citations in OpenAlex.
- Trial
- Impact of severe hypoglycemia on the heat shock and related protein response.Scientific reports · 2021Trial
- Empagliflozin inhibits the apoptosis of pancreatic β-cells through amelioration of endoplasmic reticulum (ER) stress.Metabolism open · 2026Article
- Inter-organ communication shapes human metabolic tissue states and resolves anti-diabetic drug response modes in a six-tissue microphysiological system.bioRxiv : the preprint server for biology · 2026Article
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Progress on exercise therapy in type 2 diabetes mellitus with cognitive impairment.Frontiers in sports and active living · 2026Review
- VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.Cell reports · 2025Article
- Proteostasis and Its Role in Disease Development.Cell biochemistry and biophysics · 2025Review
- Bridging Pancreatic Amyloidosis and Neurodegeneration: The Emerging Role of Amylin in Diabetic Dementia.International journal of molecular sciences · 2025Review
- Programmable protein stabilization with language model-derived peptide guides.Nature communications · 2025Article
- Review
- Scars of oxidative stress: protein carbonylation and beta cell dysfunction in diabetes.Frontiers in endocrinology · 2025Review
- Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.MedComm · 2024Review
- Programmable Protein Stabilization with Language Model-Derived Peptide Guides.Research square · 2024Article
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- The Molecular Mechanisms of the Relationship between Insulin Resistance and Parkinson's Disease Pathogenesis.Nutrients · 2023Review
- Oxidative Stress Markers and Heat Shock Proteins in Non-Obese Women with Polycystic Ovary Syndrome Are Not Elevated and Show No Correlation with Vitamin D.Biomedicines · 2023Article
- Article
- Podocyte-specific deletion of ubiquitin carboxyl-terminal hydrolase L1 causes podocyte injury by inducing endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe islet in type 2 diabetes is characterized by β-cell apoptosis, β-cell endoplasmic reticulum stress, and islet amyloid deposits derived from islet amyloid polypeptide (IAPP). Toxic oligomers of IAPP form intracellularly in β-cells in humans with type 2 diabetes, suggesting impaired clearance of misfolded proteins. In this study, we investigated whether human-IAPP (h-IAPP) disrupts the endoplasmic reticulum-associated degradation/ubiquitin/proteasome system. RESEARCH DESIGN AND
methodsWe used pancreatic tissue from humans with and without type 2 diabetes, isolated islets from h-IAPP transgenic rats, isolated human islets, and INS 832/13 cells transduced with adenoviruses expressing either h-IAPP or a comparable expression of rodent-IAPP. Immunofluorescence and Western blotting were used to detect polyubiquitinated proteins and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) protein levels. Proteasome activity was measured in isolated rat and human islets. UCH-L1 was knocked down by small-interfering RNA in INS 832/13 cells and apoptosis was evaluated.
resultsWe report accumulation of polyubiquinated proteins and UCH-L1 deficiency in β-cells of humans with type 2 diabetes. These findings were reproduced by expression of oligomeric h-IAPP but not soluble rat-IAPP. Downregulation of UCH-L1 expression and activity to reproduce that caused by h-IAPP in β-cells induced endoplasmic reticulum stress leading to apoptosis.
conclusionsOur results indicate that defective protein degradation in β-cells in type 2 diabetes can, at least in part, be attributed to misfolded h-IAPP leading to UCH-L1 deficiency, which in turn further compromises β-cell viability.
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What OpenQuestion holds
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.