Evidence map›Paper›PMID 28752047›Full record

ArticleMolecular metabolism2017

Amyloid formation disrupts the balance between interleukin-1β and interleukin-1 receptor antagonist in human islets.

Queenie Hui, Ali Asadi, Yoo Jin Park, Timothy J Kieffer, Ziliang Ao, Garth L Warnock, Lucy Marzban

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 28 citations in OpenAlex.

  1. Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Membrane Vesicles ofMicroorganisms · 2025
    Article
  3. Observational
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.Advances in experimental medicine and biology · 2021
    Article
  12. Article
  13. Article
  14. Immune regulation of islet homeostasis and adaptation.Journal of molecular cell biology · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Islet inflammation in type 2 diabetes.Seminars in immunopathology · 2019
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Queenie HuiDepartment of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Ali AsadiDepartment of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Yoo Jin ParkDepartment of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Timothy J KiefferDepartment of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Ziliang AoDepartment of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Garth L WarnockDepartment of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Lucy MarzbanDepartment of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: lucy.marzban@ubc.ca.
University of British Columbia · CA

Funding

CIHR MOP-126204
6 · The paper itself

Abstract

objectivesβ-cell dysfunction and apoptosis associated with islet inflammation play a key role in the pathogenesis of type 2 diabetes (T2D). Growing evidence suggests that islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and β-cell death in T2D. We recently showed the role of interleukin-1β (IL-1β)/Fas/caspase-8 apoptotic pathway in amyloid-induced β-cell death. In this study, we used human islets in culture as an

methodsIsolated human islets (n = 10 donors) were cultured in elevated glucose (to form amyloid) with or without a neutralizing human IL-1β antibody for up to 7 days. Parallel studies were performed with human islets in which amyloid formation was prevented by adeno-siRNA-mediated suppression of hIAPP expression (as control). β-cell levels of IL-1Ra, Fas, apoptosis as well as islet function, insulin- and amyloid-positive areas, and IL-1Ra release were assessed.

resultsProgressive amyloid formation in human islets during culture was associated with alterations in IL-1Ra. Islet IL-1Ra levels were higher at early stages but were markedly reduced at later stages of amyloid formation. Furthermore, IL-1Ra release from human islets was reduced during 7-day culture in a time-dependent manner. These changes in IL-1Ra production and release from human islets during amyloid formation adversely correlated with islet IL-1β levels, β-cell Fas expression and apoptosis. Treatment with IL-1β neutralizing antibody markedly reduced amyloid-induced β-cell Fas expression and apoptosis, thereby improving islet β-cell survival and function during culture.

conclusionsThese data suggest that amyloid formation impairs the balance between IL-1β and IL-1Ra in islets by increasing IL-1β production and reducing IL-1Ra levels thereby promoting β-cell dysfunction and death. Restoring the IL-1β/IL-1Ra ratio may provide an effective strategy to protect islet β-cells from amyloid toxicity in T2D.

Indexed as

ApoptosisAdolescentAdultAmyloidAnimalsCaspase 8Cell LineCells, CulturedFas Ligand ProteinHumansInsulin-Secreting CellsInterleukin-1betaInterleukin 1 Receptor Antagonist ProteinMiceMiddle AgedAmyloidCaspase 8Fas Ligand ProteinInterleukin-1betaInterleukin 1 Receptor Antagonist ProteinAmylinBSA, bovine serum albuminER, endoplasmic reticulumFBS, fetal bovine serumhIAPP, human islet amyloid polypeptideIL-1R1, IL-1 receptor type IIL-1Ra, IL-1 receptor antagonistIL-1β, interleukin-1βInterleukin-1 receptor antagonistInterleukin-1βIslet amyloidIslet amyloid polypeptideIslet inflammationKRB, Krebs–Ringer bicarbonatenIL1β, neutralizing IL-1βPFA, paraformaldehyderIAPP, rat islet amyloid polypeptideT2D, type 2 diabetesType 2 diabetesβ-cell apoptosis

Identifiers

PMID28752047
PMCPMC5518725
OpenAlexW2619988830

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.