ArticleThe American journal of pathology2010
Evidence for proteotoxicity in beta cells in type 2 diabetes: toxic islet amyloid polypeptide oligomers form intracellularly in the secretory pathway.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
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Who cites it
120 citing papers in PubMed, 225 citations in OpenAlex.
- Empagliflozin inhibits the apoptosis of pancreatic β-cells through amelioration of endoplasmic reticulum (ER) stress.Metabolism open · 2026Article
- Janus Polymeric Nanorods Inhibit human Amylin Oligomerization and Fibrillation for Potential Type 2 Diabetes Treatment.Small science · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- In vitro, cellular and in vivo studies of amyloid oligomers structure and toxicity: Challenges and advances.Protein science : a publication of the Protein Society · 2026Review
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Inhibition of Human Amylin Aggregation:ACS omega · 2025Article
- Effect of Copper-Catalyzed Oxidation on the Aggregation of the Islet Amyloid Polypeptide.Antioxidants (Basel, Switzerland) · 2025Article
- Review
- Anionic Lipid Catalyzes the Generation of Cytotoxic Insulin Oligomers.Biomolecules · 2025Article
- Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides.Membranes · 2025Article
- Determinants for Substoichiometric Inhibition of IAPP and Aβ Amyloid Aggregations by Bri2 BRICHOS.ACS chemical neuroscience · 2025Article
- Deuterium trafficking, mitochondrial dysfunction, copper homeostasis, and neurodegenerative disease.Frontiers in molecular biosciences · 2025Review
- Role of the extracellular matrix in amylin aggregation: Opportunities for improved therapy in type 2 diabetes mellitus.Journal of biosciences · 2025Review
- IAPP - oligomerisation levels in plasma of people with type 2 diabetes.Scientific reports · 2024Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Human islet amyloid polypeptide-induced β-cell cytotoxicity is linked to formation of α-sheet structure.Protein science : a publication of the Protein Society · 2024Article
- Mitochondria and Oxidative Stress as a Link between Alzheimer's Disease and Diabetes Mellitus.International journal of molecular sciences · 2023Review
- The potential role of human islet amyloid polypeptide in type 2 diabetes mellitus and Alzheimer's diseases.Diabetology & metabolic syndrome · 2023Review
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.Frontiers in endocrinology · 2023Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The islet in type 2 diabetes mellitus (T2DM) is characterized by a deficit in beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by beta cells. It is increasingly appreciated that the toxic form of amyloidogenic proteins is not amyloid but smaller membrane-permeant oligomers. Using an antibody specific for toxic oligomers and cryo-immunogold labeling in human IAPP transgenic mice, human insulinoma and pancreas from humans with and without T2DM, we sought to establish the abundance and sites of formation of IAPP toxic oligomers. We conclude that IAPP toxic oligomers are formed intracellularly within the secretory pathway in T2DM. Most striking, IAPP toxic oligomers appear to disrupt membranes of the secretory pathway, and then when adjacent to mitochondria, disrupt mitochondrial membranes. Toxic oligomer-induced secretory pathway and mitochondrial membrane disruption is a novel mechanism to account for cellular dysfunction and apoptosis in T2DM.
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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.