ArticleProceedings of the National Academy of Sciences of the United States of America2013
Islet amyloid polypeptide toxicity and membrane interactions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 147 citations in OpenAlex.
- Structural and morphological dynamics of "on-path" and "off-path" oligomers of human islet amyloid polypeptide.Protein science : a publication of the Protein Society · 2026Article
- A structural model of toxic amyloid oligomers involved in type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mammals that can develop type 2 diabetes have a similarly structured β-sheet amyloid oligomer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- O-glycosylated peptides curtail the aggregation and toxicity of human islet amyloid polypeptide.Communications biology · 2025Article
- The Structure of Human IAPP Fibrils Reflects Membrane and pH Conditions.Journal of the American Chemical Society · 2025Article
- Deuterium trafficking, mitochondrial dysfunction, copper homeostasis, and neurodegenerative disease.Frontiers in molecular biosciences · 2025Review
- Effect of a SARS-CoV-2 Protein Fragment on the Amyloidogenic Propensity of Human Islet Amyloid Polypeptide.ACS chemical neuroscience · 2024Article
- Immunotherapy for Parkinson's Disease and Alzheimer's Disease: A Promising Disease-Modifying Therapy.Cells · 2024Review
- Modulation of Lipid Dynamics in the β-Amyloid Aggregates Induced Membrane Fragmentation.The journal of physical chemistry. B · 2024Article
- Fluorescence Resonance Energy Transfer to Detect Plasma Membrane Perturbations in Giant Plasma Membrane Vesicles.Bio-protocol · 2023Article
- Impact of CaBiochimica et biophysica acta. Biomembranes · 2023Article
- Interspecies Variation Affects Islet Amyloid Polypeptide Membrane Binding.Journal of the American Society for Mass Spectrometry · 2023Article
- Lipid oxidation controls peptide self-assembly near membranes through a surface attraction mechanism.Chemical science · 2023Article
- Correlation analysis between immune-related genes and cell infiltration revealed prostate cancer immunotherapy biomarkers linked to T cells gamma delta.Scientific reports · 2023Article
- Fibril elongation by human islet amyloid polypeptide is the main event linking aggregation to membrane damage.BBA advances · 2023Article
- Substoichiometric Inhibition of Insulin against IAPP Aggregation Is Attenuated by the Incompletely Processed N-Terminus of proIAPP.ACS chemical neuroscience · 2022Article
- Copper chelating cyclic peptidomimetic inhibits Aβ fibrillogenesis.RSC medicinal chemistry · 2022Article
- Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas.Molecules (Basel, Switzerland) · 2022Review
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- Molecular dynamics study of water channels in natural and synthetic amyloid-β fibrils.The Journal of chemical physics · 2021Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Islet amyloid polypeptide (IAPP) is responsible for amyloid formation in type 2 diabetes and contributes to the failure of islet cell transplants, however the mechanisms of IAPP-induced cytotoxicity are not known. Interactions with model anionic membranes are known to catalyze IAPP amyloid formation in vitro. Human IAPP damages anionic membranes, promoting vesicle leakage, but the features that control IAPP-membrane interactions and the connection with cellular toxicity are not clear. Kinetic studies with wild-type IAPP and IAPP mutants demonstrate that membrane leakage is induced by prefibrillar IAPP species and continues over the course of amyloid formation, correlating additional membrane disruption with fibril growth. Analyses of a set of designed mutants reveal that membrane leakage does not require the formation of β-sheet or α-helical structures. A His-18 to Arg substitution enhances leakage, whereas replacement of all of the aromatic residues via a triple leucine mutant has no effect. Biophysical measurements in conjunction with cytotoxicity studies show that nonamyloidogenic rat IAPP is as effective as human IAPP at disrupting standard anionic model membranes under conditions where rat IAPP does not induce cellular toxicity. Similar results are obtained with more complex model membranes, including ternary systems that contain cholesterol and are capable of forming lipid rafts. A designed point mutant, I26P-IAPP; a designed double mutant, G24P, I26P-IAPP; a double N-methylated variant; and pramlintide, a US Food and Drug Administration-approved IAPP variant all induce membrane leakage, but are not cytotoxic, showing that there is no one-to-one relationship between disruption of model membranes and induction of cellular toxicity.
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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.