ArticleScientific reports2015
Inhibition of IAPP aggregation by insulin depends on the insulin oligomeric state regulated by zinc ion concentration.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 61 citations in OpenAlex.
- Impact of zinc and chromium deficiency on gene expression in type 2 diabetes mellitus.Scientific reports · 2025Article
- Amyloid-β disrupts APP-regulated protein aggregation and dissociation from recycling endosomal membranes.The EMBO journal · 2025Article
- Determinants for Substoichiometric Inhibition of IAPP and Aβ Amyloid Aggregations by Bri2 BRICHOS.ACS chemical neuroscience · 2025Article
- Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.Biophysical chemistry · 2024Review
- Zinc and pH modulate the ability of insulin to inhibit aggregation of islet amyloid polypeptide.Communications biology · 2024Article
- Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic β cells.Biophysical chemistry · 2024Article
- Realization of Amyloid-like Aggregation as a Common Cause for Pathogenesis in Diseases.Life (Basel, Switzerland) · 2023Review
- Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus.Journal of pharmaceutical analysis · 2022Review
- Substoichiometric Inhibition of Insulin against IAPP Aggregation Is Attenuated by the Incompletely Processed N-Terminus of proIAPP.ACS chemical neuroscience · 2022Article
- Linking hIAPP misfolding and aggregation with type 2 diabetes mellitus: a structural perspective.Bioscience reports · 2022Review
- Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus.Life (Basel, Switzerland) · 2022Review
- Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas.Molecules (Basel, Switzerland) · 2022Review
- Inside the Insulin Secretory Granule.Metabolites · 2021Review
- Loss of Znt8 function in diabetes mellitus: risk or benefit?Molecular and cellular biochemistry · 2021Review
- Undercover Toxic Ménage à Trois of Amylin, Copper (II) and Metformin in Human Embryonic Kidney Cells.Pharmaceutics · 2021Article
- Regulation of divalent metal ions to the aggregation and membrane damage of human islet amyloid polypeptide oligomers.RSC advances · 2021Article
- α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine.Chemical science · 2021Article
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- From Zn(II) to Cu(II) Detection by MRI Using Metal-Based Probes: Current Progress and Challenges.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Liquid-liquid phase separation of type II diabetes-associated IAPP initiates hydrogelation and aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
While islet amyloid polypeptide (IAPP) aggregation is associated with β-cell death in type-II diabetes (T2D), environmental elements of β-cell granules - e.g. high concentrations of insulin and Zn(2+) - inhibit IAPP aggregation in healthy individuals. The inhibition by insulin is experimentally known, but the role of Zn(2+) is controversial as both correlations and anti-correlations at the population level are observed between T2D risk and the activity of a β-cell specific zinc ion transporter, ZnT8. Since Zn(2+) concentration determines insulin oligomer equilibrium, we computationally investigated interactions of IAPP with different insulin oligomers and compared with IAPP homodimer formation. We found that IAPP binding with insulin oligomers competes with the formation of both higher-molecular-weight insulin oligomers and IAPP homodimers. Therefore, zinc deficiency due to loss-of-function ZnT8 mutations shifts insulin oligomer equilibrium toward zinc-free monomers and dimers, which bind IAPP monomers more efficiently compared to zinc-bound hexamers. The hetero-molecular complex formation prevents IAPP from self-association and subsequent aggregation, reducing T2D risk.
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