ArticleBiochemistry2015
Mutational analysis of the ability of resveratrol to inhibit amyloid formation by islet amyloid polypeptide: critical evaluation of the importance of aromatic-inhibitor and histidine-inhibitor interactions.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 60 citations in OpenAlex.
- Use of Small Organic Molecules to Improve Pancreatic Beta Cell Resilience to IAPP-Induced Proteotoxic Stress.International journal of molecular sciences · 2026Review
- Molecular Mechanisms of Islet Amyloid Polypeptide Aggregation: Towards Chemical Strategies to Prevent Amyloid Formation and to Design Non-Aggregating Peptide Therapeutics.International journal of molecular sciences · 2026Review
- 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
- Resveratrol modulates pancreatic proteotoxic stress and metabolic dysfunction in human IAPP transgenic mice.Frontiers in endocrinology · 2026Article
- Plant-Based Inhibitors of Protein Aggregation.Biomolecules · 2025Review
- Resveratrol protects pancreatic beta cell and hippocampal cells from the aggregate-prone capacity of hIAPP.Scientific reports · 2024Article
- Exploration of Resveratrol as a Potent Modulator of α-Synuclein Fibril Formation.ACS chemical neuroscience · 2024Article
- Inhibition of β-Amyloid Aggregation in Alzheimer's Disease: The Key Role of (Pro)electrophilic Warheads.ACS medicinal chemistry letters · 2022Article
- Urolithin B: Two-way attack on IAPP proteotoxicity with implications for diabetes.Frontiers in endocrinology · 2022Article
- Novel Human Insulin Isoforms and Cα-Peptide Product in Islets of Langerhans and Choroid Plexus.Diabetes · 2021Article
- Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in a Transgenic Rat Model of Type 2 Diabetes.ACS pharmacology & translational science · 2021Article
- Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review.Frontiers in pharmacology · 2021Review
- Analysis of Proline Substitutions Reveals the Plasticity and Sequence Sensitivity of Human IAPP Amyloidogenicity and Toxicity.Biochemistry · 2020Article
- Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease.Frontiers in molecular neuroscience · 2020Review
- Zinc boosts EGCG's hIAPP amyloid Inhibition both in solution and membrane.Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- Pre-structured hydrophobic peptide β-strands: A universal amyloid trap?Archives of biochemistry and biophysics · 2019Review
- Inhibition of protein misfolding and aggregation by natural phenolic compounds.Cellular and molecular life sciences : CMLS · 2018Review
- Natural product-based amyloid inhibitors.Biochemical pharmacology · 2017Review
- β-Hairpin mimics containing a piperidine-pyrrolidine scaffold modulate the β-amyloid aggregation process preserving the monomer species.Chemical science · 2017Article
- Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide: MECHANISTIC DETAILS STUDIED BY SPECTROSCOPY IN COMBINATION WITH MICROSCOPY.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The process of amyloid formation by the normally soluble hormone islet amyloid polypeptide (IAPP) contributes to β-cell death in type 2 diabetes and in islet transplants. There are no clinically approved inhibitors of islet amyloidosis, and the mode of action of existing inhibitors is not well-understood. Resveratrol, a natural polyphenol, has been reported to inhibit amyloid formation by IAPP and by the Alzheimer's disease Aβ peptide. The mechanism of action of this compound is not known, nor is its mode of interaction with IAPP. In this study, we use a series of IAPP variants to examine possible interactions between resveratrol and IAPP. Fluorescence assays, transmission electron microscopy, and mass spectrometry demonstrate that resveratrol is much less effective as an inhibitor of IAPP amyloid formation than the polyphenol (-)-epigallocatechin 3-gallate (EGCG) and, unlike EGCG, does not significantly disaggregate preformed IAPP amyloid fibrils. Resveratrol is also shown to interfere with thioflavin-T assays. His-18 mutants, a truncation mutant, mutants of each of the aromatic residues, and mutants of Arg-11 of IAPP were examined. Mutation of His to Gln or Leu weakens the ability of resveratrol to inhibit amyloid formation by IAPP, as do mutations of Arg-11, Phe-15, or Tyr-37 to Leu, and truncation to form the variant Ac 8-37-IAPP, which removes the first seven residues to eliminate Lys-1 and the N-terminal amino group. In contrast, replacement of Phe-23 with Leu has a smaller effect. The data highlight Phe-15, His-18, and Tyr-37 as being important for IAPP-resveratrol interactions and are consistent with a potential role of the N-terminus and Arg-11 in polypeptide-resveratrol interactions.
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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.