ArticleThe Journal of biological chemistry2012
Islet amyloid polypeptide triggers limited complement activation and binds complement inhibitor C4b-binding protein, which enhances fibril formation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Complement in metabolic disease: metaflammation and a two-edged sword.Seminars in immunopathology · 2021Review
- Serum complement C3 and islet β-cell function in patients with type 2 diabetes: A 4.6-year prospective follow-up study.Endocrine · 2020Article
- The human serum protein C4b-binding protein inhibits pancreatic IAPP-induced inflammasome activation.Diabetologia · 2017Article
- C4b-binding Protein Protects β-Cells from Islet Amyloid Polypeptide-induced Cytotoxicity.The Journal of biological chemistry · 2016Article
- Proteomic Analyses for the Global S-Nitrosylated Proteins in the Brain Tissues of Different Human Prion Diseases.Molecular neurobiology · 2016Article
- Article
- Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease.The Journal of experimental medicine · 2014Article
- The role of the complement system in metabolic organs and metabolic diseases.Seminars in immunology · 2013Review
- Article
- Cartilage oligomeric matrix protein-induced complement activation in systemic sclerosis.Arthritis research & therapy · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Islet amyloid polypeptide (IAPP) is synthesized in pancreatic β-cells and co-secreted with insulin. Aggregation and formation of IAPP-amyloid play a critical role in β-cell death in type 2 diabetic patients. Because Aβ-fibrils in Alzheimer disease activate the complement system, we have here investigated specific interactions between IAPP and complement factors. IAPP fibrils triggered limited activation of complement in vitro, involving both the classical and the alternative pathways. Direct binding assays confirmed that IAPP fibrils interact with globular head domains of complement initiator C1q. Furthermore, IAPP also bound complement inhibitors factor H and C4b-binding protein (C4BP). Recombinant C4BP mutants were used to show that complement control protein (CCP) domains 8 and 2 of the α-chain were responsible for the strong, hydrophobic binding of C4BP to IAPP. Immunostaining of pancreatic sections from type 2 diabetic patients revealed the presence of complement factors in the islets and varying degree of co-localization between IAPP fibrils and C1q, C3d, as well as C4BP and factor H but not membrane attack complex. Furthermore, C4BP enhanced formation of IAPP fibrils in vitro. We conclude that C4BP binds to IAPP thereby limiting complement activation and may be enhancing formation of IAPP fibrils from cytotoxic oligomers.
Indexed as
Identifiers
What OpenQuestion holds
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.