ArticleDiabetologia2016
The S20G substitution in hIAPP is more amyloidogenic and cytotoxic than wild-type hIAPP in mouse islets.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Mitochondrial dysfunction-driven inflammation and β-Cell apoptosis in type 2 diabetes mellitus: mechanistic insights and therapeutic implications.Molecular biology reports · 2026Review
- 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
- Experimental and computational analysis of the basis for accelerated amyloid formation by a disease linked mutant of human islet amyloid polypeptide.Protein science : a publication of the Protein Society · 2025Article
- Monomer binding modes of small molecules that modulate the kinetics of hIAPP amyloid formation.bioRxiv : the preprint server for biology · 2025Article
- Peptidylglycine alpha-amidating monooxygenase is important in mice for beta-cell cilia formation and insulin secretion but promotes diabetes risk through beta-cell independent mechanisms.Molecular metabolism · 2025Article
- Article
- Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis.ACS bio & med chem Au · 2024Review
- Experimental Insights into Conformational Ensembles of Assembled β-Sheet Peptides.ACS central science · 2023Article
- Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes.Frontiers in endocrinology · 2023Review
- Analysis of Sheep and Goat IAPP Provides Insight into IAPP Amyloidogenicity and Cytotoxicity.Biochemistry · 2022Article
- Molecular insights into the oligomerization dynamics and conformations of amyloidogenic and non-amyloidogenic amylin from discrete molecular dynamics simulations.Physical chemistry chemical physics : PCCP · 2022Article
- Pathophysiology, phenotypes and management of type 2 diabetes mellitus in Indian and Chinese populations.Nature reviews. Endocrinology · 2022Review
- Factors That Contribute to hIAPP Amyloidosis in Type 2 Diabetes Mellitus.Life (Basel, Switzerland) · 2022Review
- Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly.Nature communications · 2022Article
- Cryo-EM structures of hIAPP fibrils seeded by patient-extracted fibrils reveal new polymorphs and conserved fibril cores.Nature structural & molecular biology · 2021Article
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
- Low concentration IL-1β promotes islet amyloid formation by increasing hIAPP release from humanised mouse islets in vitro.Diabetologia · 2020Article
- Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly.Nature structural & molecular biology · 2020Article
- Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils.Nature structural & molecular biology · 2020Article
- Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils.Nature structural & molecular biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisThe S20G human islet amyloid polypeptide (hIAPP) substitution is associated with an earlier onset of type 2 diabetes in humans. Studies of synthetic S20G hIAPP in cell-free systems and immortalised beta cells have suggested that this may be due to increased hIAPP amyloidogenicity and cytotoxicity. Thus, using primary islets from mice with endogenous S20G hIAPP expression, we sought to determine whether the S20G gene mutation leads to increased amyloid-induced toxicity, beta cell loss and reduced beta cell function.
methodsIslets from mice in which mouse Iapp was replaced with human wild-type or S20G hIAPP were isolated and cultured in vitro under amyloid-forming conditions. Levels of insulin and hIAPP mRNA and protein, amyloid deposition and beta cell apoptosis and area, as well as glucose-stimulated insulin and hIAPP secretion, were quantified.
resultsIslets expressing S20G hIAPP cultured in 16.7 mmol/l glucose demonstrated increased amyloid deposition and beta cell apoptosis, reduced beta cell area, decreased insulin content and diminished glucose-stimulated insulin secretion, compared with islets expressing wild-type hIAPP. Amyloid deposition and beta cell apoptosis were also increased when S20G islets were cultured in 11.1 mmol/l glucose (the concentration that is thought to be physiological for mouse islets). CONCLUSIONS/
interpretationS20G hIAPP reduces beta cell number and function, thereby possibly explaining the earlier onset of type 2 diabetes in individuals carrying this gene mutation.
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