Evidence map›Paper›PMID 29478918›Full record

ArticleMolecular metabolism2018

Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

H L Kammoun, T L Allen, D C Henstridge, S Barre, R C Coll, G I Lancaster, L Cron, S Reibe, J Y Chan, M Bensellam and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% 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, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
  2. Translational Geroscience Strategies for Delaying Multimorbidity.ACS pharmacology & translational science · 2026
    Review
  3. Review
  4. Review
  5. Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022
    Article
  6. Article
  7. Islet Inflammation and β Cell Dysfunction in Type 2 Diabetes.Handbook of experimental pharmacology · 2022
    Review
  8. Emodin Alleviates High-Glucose-Induced PancreaticEvidence-based complementary and alternative medicine : eCAM · 2022
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Carvacrol may alleviate vascular inflammation in diabetic db/db mice.International journal of molecular medicine · 2020
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases.Frontiers in molecular neuroscience · 2018
    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

16 authors at 5 institutions in 2 countries.

H L KammounCellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia. Electronic address: helene.kammoun@baker.edu.au.
T L AllenCellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia.
D C HenstridgeCellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia.
S BarreCellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia.
R C CollInstitute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.
G I LancasterCellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia.
L CronDivision of Diabetes & Metabolism, Garvan Institute of Medical Research, Sydney, Australia.
S ReibeDivision of Diabetes & Metabolism, Garvan Institute of Medical Research, Sydney, Australia.
J Y ChanDivision of Diabetes & Metabolism, Garvan Institute of Medical Research, Sydney, Australia.
M BensellamDivision of Diabetes & Metabolism, Garvan Institute of Medical Research, Sydney, Australia.
D R LaybuttDivision of Diabetes & Metabolism, Garvan Institute of Medical Research, Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
M S ButlerInstitute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.
A A B RobertsonInstitute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.
L A O'NeillInflammation research, Trinity Biomedical Sciences Institute, Dublin, Ireland.
M A CooperInstitute for Molecular Bioscience, The University of Queensland, St Lucia, Australia.
M A FebbraioCellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia; Division of Diabetes & Metabolism, Garvan Institute of Medical Research, Sydney, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia. Electronic address: m.febbraio@garvan.org.au.
Baker Heart and Diabetes Institute · AUGarvan Institute of Medical Research · AUUniversity of Queensland · AUTrinity College Dublin · IEUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesType 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1β (IL-1β) have been implicated in pancreatic β cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic β cell death could allow for selective T2D treatment without compromising all IL-1β-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic β cell death, thereby preventing the onset of T2D.

methodsDiabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic β cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention.

resultsMCC950 was a potent inhibitor of NLRP3-induced IL-1β in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activation of this pathway nor increased levels of its target IL-1β.

conclusionsNLRP3 driven-pancreatic IL-1β inflammation does not play a key role in the pathogenesis of the db/db murine model of T2D.

Indexed as

AnimalsAnti-Inflammatory AgentsCells, CulturedDiabetes Mellitus, Type 2FuransHeterocyclic Compounds, 4 or More RingsHypoglycemic AgentsIndenesInsulin-Secreting CellsInterleukin-1betaMiceNLR Family, Pyrin Domain-Containing 3 ProteinSulfonamidesSulfonesAnti-Inflammatory AgentsFuransHeterocyclic Compounds, 4 or More RingsHypoglycemic AgentsIndenesInterleukin-1betaN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseSulfonamidesSulfonesdb/db miceInflammasomeInterleukin-1βMCC950Type 2 diabetes

Identifiers

PMID29478918
PMCPMC5985230
OpenAlexW2790608991

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.