Evidence map›Paper›PMID 20089617›Full record

ArticleThe Journal of clinical endocrinology and metabolism2010

12-Lipoxygenase Products Reduce Insulin Secretion and {beta}-Cell Viability in Human Islets.

K Ma, C S Nunemaker, R Wu, S K Chakrabarti, D A Taylor-Fishwick, J L Nadler

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 111 citations in OpenAlex.

  1. Article
  2. Article
  3. 12/15-lipoxygenase orchestrates murine wound healing via PPARγ-activating oxylipins acting holistically to dampen inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  5. Frontiers in pharmacology · 2024
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  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
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  12. Article
  13. Review
  14. Review
  15. Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022
    Review
  16. Article
  17. Article
  18. Review
  19. The Impact of the CaBiomolecules · 2021
    Review
  20. Review

16 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

K MaStrelitz Diabetes Center, Department of Internal Medicine, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 410, Norfolk, Virginia 23507, USA.
C S Nunemaker
R Wu
S K Chakrabarti
D A Taylor-Fishwick
J L Nadler
Eastern Virginia Medical School · USUniversity of Virginia · US

Funding

Lipid Mediators in Pancreatic Islet DysfunctionR01DK055240 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI NADLER, JERRY L. · 1998 to 2010
$1.6M
Assessing and Improving Pancreatic Islet Viability and FunctionK01DK081621 · NIDDK · UNIVERSITY OF VIRGINIA · PI NUNEMAKER, CRAIG S · 2008 to 2010
$324k
NIDDK NIH HHS K01 DK081621NIDDK NIH HHS R01 DK055240NIDDK NIH HHS R-01 DK 55240
6 · The paper itself

Abstract

contextInflammation is increasingly recognized as an important contributing factor in diabetes mellitus. Lipoxygenases (LOs) produce active lipids that promote inflammatory damage by catalyzing the oxidation of linoleic and arachidonic acid, and LO is expressed in rodent and human islets. Little is known about the differential effect of the various hydroxyeicosatetraenoic acids (HETEs) that result from LO activity in human islets.

objectiveWe compared the effects of 12-LO products on human islet viability and function.

designHuman islets were treated with stable compounds derived from LOs: 12(S)-HETE, 15HETE, 12HPETE, and 12RHETE and then examined for insulin secretion and islet viability. The p38-MAPK (p38) and JNK stress-activated pathways were investigated as mechanisms of 12-LO-mediated islet inhibition in rodent and human islets.

resultsInsulin secretion was consistently reduced by 12(S)-HETE and 12HPETE. 12(S)-HETE at 1 nm reduced viability activity by 32% measured by MTT assay and increased cell death by 50% at 100 nm in human islets. These effects were partially reversed with lisofylline, a small-molecule antiinflammatory compound that protects mitochondrial function. 12(S)-HETE increased phosphorylated p38-MAPK (pp38) protein activity in human islets. Injecting 12-LO siRNA into C57BL/6 mice reduced 12-LO and pp38-MAPK protein levels in mouse islets. The addition of proinflammatory cytokines increased pp38 levels in normal mouse islets but not in siRNA-treated islets.

conclusionsThese data suggest that 12(S)-HETE reduces insulin secretion and increases cell death in human islets. The 12-LO pathway is present in human islets, and expression is up-regulated by inflammatory cytokines. Reduction of 12-LO activity could thus provide a new therapeutic approach to protect human beta-cells from inflammatory injury.

Indexed as

12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimalsApoptosisArachidonate 12-LipoxygenaseCell SurvivalHumansInsulinInsulin-Secreting CellsInsulin SecretionMaleMiceMice, Inbred C57BLp38 Mitogen-Activated Protein KinasesPentoxifyllinePhosphorylation12-Hydroxy-5,8,10,14-eicosatetraenoic AcidArachidonate 12-LipoxygenaseInsulinlisofyllinep38 Mitogen-Activated Protein KinasesPentoxifylline

Identifiers

PMID20089617
PMCPMC2840856
OpenAlexW2165615152

What Socratic holds

Textmetadata
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 Socratic graph.