ArticleThe Journal of clinical investigation2014
Human IAPP-induced pancreatic β cell toxicity and its regulation by autophagy.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
112 citing papers in PubMed, 2 syntheses or guidelines pooled it, 171 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Impact of Stabilizing Osmolytes on the Conformational Dynamics of Human and Rat Islet Amyloid Polypeptides.Proteins · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- A Metabolomics-Based Strategy for Identifying Endogenous Inhibitors of IAPP Aggregation.Metabolites · 2026Article
- Mitochondrial dysfunction-driven inflammation and β-Cell apoptosis in type 2 diabetes mellitus: mechanistic insights and therapeutic implications.Molecular biology reports · 2026Review
- Physiological Implications of Pancreatic Amyloid Polypeptide Aggregation and Its Inhibition by Melatonin.International journal of molecular sciences · 2026Review
- Evaluation of distinct and similar pathological features between diabetes and Alzheimer's disease.EXCLI journal · 2026Review
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- Cross-seeding of IAPP and Aβ42: A review of the molecular link between type 2 diabetes and Alzheimer's disease.Metabolic brain disease · 2025Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Amylin Receptor 1 Mutagenesis Revealed a Potential Role of Calcitonin Serine 29 in Receptor Interaction.Biomedicines · 2025Article
- Proteostasis signatures in human diseases.PLoS computational biology · 2025Article
- Bridging Pancreatic Amyloidosis and Neurodegeneration: The Emerging Role of Amylin in Diabetic Dementia.International journal of molecular sciences · 2025Review
- Pancreatic β-cell Dysfunction and Diabetes.Juntendo medical journal · 2025Review
- Small HSPs at the crossroad between protein aggregation, autophagy and unconventional secretion: clinical implications and potential therapeutic opportunities in the context of neurodegenerative diseases.Frontiers in cell and developmental biology · 2025Review
- Review
- Role of β-cell autophagy in β-cell physiology and the development of diabetes.Journal of diabetes investigation · 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
- Human IAPP is a contributor to painful diabetic peripheral neuropathy.The Journal of clinical investigation · 2023Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic islets in patients with type 2 diabetes mellitus (T2DM) are characterized by loss of β cells and formation of amyloid deposits derived from islet amyloid polypeptide (IAPP). Here we demonstrated that treatment of INS-1 cells with human IAPP (hIAPP) enhances cell death, inhibits cytoproliferation, and increases autophagosome formation. Furthermore, inhibition of autophagy increased the vulnerability of β cells to the cytotoxic effects of hIAPP. Based on these in vitro findings, we examined the pathogenic role of hIAPP and its relation to autophagy in hIAPP-knockin mice. In animals fed a standard diet, hIAPP had no toxic effects on β cell function; however, hIAPP-knockin mice did not exhibit a high-fat-diet-induced compensatory increase in β cell mass, which was due to limited β cell proliferation and enhanced β cell apoptosis. Importantly, expression of hIAPP in mice with a β cell-specific autophagy defect resulted in substantial deterioration of glucose tolerance and dispersed cytoplasmic expression of p62-associated toxic oligomers, which were otherwise sequestrated within p62-positive inclusions. Together, our results indicate that increased insulin resistance in combination with reduced autophagy may enhance the toxic potential of hIAPP and enhance β cell dysfunction and progression of 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.