Evidence map›Paper›PMID 25861744›Full record

ArticleCell calcium2015

Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets.

Farhan M Qureshi, Eden A Dejene, Kathryn L Corbin, Craig S Nunemaker

Open access · greenAbstract read
In one paragraph

Article in Cell calcium, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Trial
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  11. Review
  12. Article
  13. Reflections on undergraduate research mentoring.Biophysicist (Rockville, Md.) · 2020
    Article
  14. Calpain inhibitor and ibudilast rescue β cell functions in a cellular model of Wolfram syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  15. Article
  16. Article
  17. Review
  18. Cytokine-mediated changes in KScientific reports · 2018
    Article
  19. Article
  20. Pancreatic islet inflammation: an emerging role for chemokines.Journal of molecular endocrinology · 2017
    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

4 authors at 1 institution in 1 country.

Farhan M Qureshi *Department of Medicine, University of Virginia, Charlottesville, VA.
Eden A Dejene *Department of Medicine, University of Virginia, Charlottesville, VA.
Kathryn L CorbinDepartment of Medicine, University of Virginia, Charlottesville, VA.
Craig S NunemakerDepartment of Medicine, University of Virginia, Charlottesville, VA.
University of Virginia · US

Funding

Low-grade Inflammation, Cytokines, and Beta-Cell Dysfunction in Type 2 DiabetesR01DK089182 · NIDDK · UNIVERSITY OF VIRGINIA · PI NUNEMAKER, CRAIG S · 2011 to 2015
$1.6M
NIDDK NIH HHS R01 DK089182NIDDK NIH HHS R01DK089182
6 · The paper itself

Abstract

In healthy pancreatic islets, glucose-stimulated changes in intracellular calcium ([Ca(2+)]i) provide a reasonable reflection of the patterns and relative amounts of insulin secretion. We report that [Ca(2+)]i in islets under stress, however, dissociates with insulin release in different ways for different stressors. Islets were exposed for 48h to a variety of stressors: cytokines (low-grade inflammation), 28mM glucose (28G, glucotoxicity), free fatty acids (FFAs, lipotoxicity), thapsigargin (ER stress), or rotenone (mitochondrial stress). We then measured [Ca(2+)]i and insulin release in parallel studies. Islets exposed to all stressors except rotenone displayed significantly elevated [Ca(2+)]i in low glucose, however, increased insulin secretion was only observed for 28G due to increased nifedipine-sensitive calcium-channel flux. Following 3-11mM glucose stimulation, all stressors substantially reduced the peak glucose-stimulated [Ca(2+)]i response (first phase). Thapsigargin and cytokines also substantially impacted aspects of calcium influx and ER calcium handling. Stressors did not significantly impact insulin secretion in 11mM glucose for any stressor, although FFAs showed a borderline reduction, which contributed to a significant decrease in the stimulation index (11:3mM glucose) observed for FFAs and also for 28G. We also clamped [Ca(2+)]i using 30mM KCl+250μM diazoxide to test the amplifying pathway. Only rotenone-treated islets showed a robust increase in 3-11mM glucose-stimulated insulin secretion under clamped conditions, suggesting that low-level mitochondrial stress might activate the metabolic amplifying pathway. We conclude that different stressors dissociate [Ca(2+)]i from insulin secretion differently: ER stressors (thapsigargin, cytokines) primarily affect [Ca(2+)]i but not conventional insulin secretion and 'metabolic' stressors (FFAs, 28G, rotenone) impacted insulin secretion.

Indexed as

AnimalsCalciumCalcium SignalingCytokinesEndoplasmic ReticulumFatty Acids, NonesterifiedGlucoseInsulinInsulin SecretionIslets of LangerhansMiceModels, AnimalStress, PhysiologicalCalciumCytokinesFatty Acids, NonesterifiedGlucoseInsulinBeta-cellsCalciumChronicCytokinesDiabetesEndoplasmic reticulumER stressFree fatty acidGlucotoxicityHigh glucoseIL-1betaIL-6InsulinInterleukinIsletsLinoleateLow-grade inflammationOleateOxidative stressPalmitateRotenoneThapsigarginUnfolded protein response

Identifiers

PMID25861744
PMCPMC4417449
OpenAlexW2095487525

What OpenQuestion holds

Textmetadata
LicenceTDM
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.