ArticleThe Journal of biological chemistry2010
Neprilysin impedes islet amyloid formation by inhibition of fibril formation rather than peptide degradation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Article
- Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic β cells.Biophysical chemistry · 2024Article
- Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena.Journal of diabetes · 2023Review
- Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus.Journal of pharmaceutical analysis · 2022Review
- Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas.Molecules (Basel, Switzerland) · 2022Review
- Proteostasis of Islet Amyloid Polypeptide: A Molecular Perspective of Risk Factors and Protective Strategies for Type II Diabetes.Chemical reviews · 2021Review
- Loss of perlecan heparan sulfate glycosaminoglycans lowers body weight and decreases islet amyloid deposition in human islet amyloid polypeptide transgenic mice.Protein engineering, design & selection : PEDS · 2019Article
- Neprilysin inhibition: a new therapeutic option for type 2 diabetes?Diabetologia · 2019Review
- Use of the PET ligand florbetapir for in vivo imaging of pancreatic islet amyloid deposits in hIAPP transgenic mice.Diabetologia · 2018Article
- Amyloid-induced β-cell dysfunction and islet inflammation are ameliorated by 4-phenylbutyrate (PBA) treatment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Apoptosis Repressor With Caspase Recruitment Domain Ameliorates Amyloid-Induced β-Cell Apoptosis and JNK Pathway Activation.Diabetes · 2017Article
- Inhibition of Insulin-Degrading Enzyme Does Not Increase Islet Amyloid Deposition in Vitro.Endocrinology · 2016Article
- Proteasome regulates turnover of toxic human amylin in pancreatic cells.The Biochemical journal · 2016Article
- Sex and Immunogen-Specific Benefits of Immunotherapy Targeting Islet Amyloid Polypeptide in Transgenic and Wild-Type Mice.Frontiers in endocrinology · 2016Article
- Matrix Metalloproteinase-9 Protects Islets from Amyloid-induced Toxicity.The Journal of biological chemistry · 2015Article
- Determination of Optimal Sample Size for Quantification of β-Cell Area, Amyloid Area and β-Cell Apoptosis in Isolated Islets.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2015Article
- Type 2 diabetes as a protein misfolding disease.Trends in molecular medicine · 2015Review
- Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer's disease.Frontiers in aging neuroscience · 2014Review
- Neprilysin deficiency protects against fat-induced insulin secretory dysfunction by maintaining calcium influx.Diabetes · 2013Article
- Matrix metalloproteinase-9 reduces islet amyloid formation by degrading islet amyloid polypeptide.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Deposition of islet amyloid polypeptide (IAPP) as islet amyloid in type 2 diabetes contributes to loss of beta-cell function and mass, yet the mechanism for its occurrence is unclear. Neprilysin is a metallopeptidase known to degrade amyloid in Alzheimer disease. We previously demonstrated neprilysin to be present in pancreatic islets and now sought to determine whether it plays a role in degrading islet amyloid. We used an in vitro model where cultured human IAPP (hIAPP) transgenic mouse islets develop amyloid and thereby have increased beta-cell apoptosis. Islet neprilysin activity was inhibited or up-regulated using a specific inhibitor or adenovirus encoding neprilysin, respectively. Following neprilysin inhibition, islet amyloid deposition and beta-cell apoptosis increased by 54 and 75%, respectively, whereas when neprilysin was up-regulated islet amyloid deposition and beta-cell apoptosis both decreased by 79%. To determine if neprilysin modulated amyloid deposition by cleaving hIAPP, analysis of hIAPP incubated with neprilysin was performed by mass spectrometry, which failed to demonstrate neprilysin-induced cleavage. Rather, neprilysin may act by reducing hIAPP fibrillogenesis, which we showed to be the case by fluorescence-based thioflavin T binding studies and electron microscopy. In summary, neprilysin decreases islet amyloid deposition by inhibiting hIAPP fibril formation, rather than degrading hIAPP. These findings suggest that targeting the role of neprilysin in IAPP fibril assembly, in addition to IAPP cleavage by other peptidases, may provide a novel approach to reduce and/or prevent islet amyloid deposition in type 2 diabetes.
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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.