Evidence map›Paper›PMID 24627477›Full record

ArticleThe Journal of biological chemistry2014

Inhibition of pancreatic β-cell Ca2+/calmodulin-dependent protein kinase II reduces glucose-stimulated calcium influx and insulin secretion, impairing glucose tolerance.

Prasanna K Dadi, Nicholas C Vierra, Alessandro Ustione, David W Piston, Roger J Colbran, David A Jacobson

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
5.0field-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

40 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. CaFrontiers in endocrinology · 2024
    Review
  9. Pharmacological reviews · 2023
    Review
  10. Article
  11. Article
  12. The functions of CaJournal of cell communication and signaling · 2023
    Review
  13. [Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022
    Article
  14. Article
  15. Heart failure in diabetes.Metabolism: clinical and experimental · 2021
    Review
  16. Article
  17. Key Metabolic Functions of β-Arrestins: Studies with Novel Mouse Models.Trends in endocrinology and metabolism: TEM · 2021
    Review
  18. Article
  19. Primary cilia control glucose homeostasis via islet paracrine interactions.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  20. Article
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 1 institution in 1 country.

Prasanna K DadiFrom the Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232.
Nicholas C Vierra
Alessandro Ustione
David W Piston
Roger J Colbran
David A Jacobson
Vanderbilt University · US

Funding

Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI ELASY, TOM A · 1986 to 2011
$28.1M
Mechanisms of CaM Kinase II Signal TransductionR01MH063232 · NIMH · VANDERBILT UNIVERSITY · PI COLBRAN, ROGER J · 2001 to 2015
$5.4M
Two-Pore-Domain Potassium Channels as Novel Targets for Modulating Islet Hormone SecretionR01DK097392 · NIDDK · VANDERBILT UNIVERSITY · PI JACOBSON, DAVID AARON · 2013 to 2022
$3.3M
Pancreatic Islets Dynamics Regulating Glucagon SecretionR01DK098659 · NIDDK · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2013 to 2016
$1.3M
Secretagogue Induced Mechanisms Regulating Islet Electrical ActivityK01DK081666 · NIDDK · VANDERBILT UNIVERSITY · PI JACOBSON, DAVID AARON · 2009 to 2012
$505k
Pancreatic beta-cell CAMKII signaling under physiological and diabetic conditionsR03DK096122 · NIDDK · VANDERBILT UNIVERSITY · PI JACOBSON, DAVID AARON · 2012 to 2013
$153k
NIDDK NIH HHS DK081666NIDDK NIH HHS DK096122NIDDK NIH HHS DK20593NIDDK NIH HHS K01 DK081666NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P60 DK020593NIDDK NIH HHS P60 DK20593NIDDK NIH HHS R01 DK098659NIDDK NIH HHS R03 DK096122NIMH NIH HHS R01 MH063232
6 · The paper itself

Abstract

Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is caused by Ca(2+) entry via voltage-dependent Ca(2+) channels. CaMKII is a key mediator and feedback regulator of Ca(2+) signaling in many tissues, but its role in β-cells is poorly understood, especially in vivo. Here, we report that mice with conditional inhibition of CaMKII in β-cells show significantly impaired glucose tolerance due to decreased GSIS. Moreover, β-cell CaMKII inhibition dramatically exacerbates glucose intolerance following exposure to a high fat diet. The impairment of islet GSIS by β-cell CaMKII inhibition is not accompanied by changes in either glucose metabolism or the activities of KATP and voltage-gated potassium channels. However, glucose-stimulated Ca(2+) entry via voltage-dependent Ca(2+) channels is reduced in islet β-cells with CaMKII inhibition, as well as in primary wild-type β-cells treated with a peptide inhibitor of CaMKII. The levels of basal β-cell cytoplasmic Ca(2+) and of endoplasmic reticulum Ca(2+) stores are also decreased by CaMKII inhibition. In addition, CaMKII inhibition suppresses glucose-stimulated action potential firing frequency. These results reveal that CaMKII is a Ca(2+) sensor with a key role as a feed-forward stimulator of β-cell Ca(2+) signals that enhance GSIS under physiological and pathological conditions.

Indexed as

Action PotentialsAnimalsBiological TransportBlotting, WesternCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium ChannelsCells, CulturedCytoplasmDoxycyclineEndoplasmic ReticulumGlucoseGlucose IntoleranceGreen Fluorescent ProteinsHomeostasisInsulinautocamptide-2-related inhibitory peptide IICalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium ChannelsDoxycyclineGlucoseGreen Fluorescent ProteinsInsulinPeptidesPotassium ChannelsCalcium ChannelsCalcium ImagingCaMKIIDiabetesInsulinInsulin SecretionIsletPancreatic Islets

Identifiers

PMID24627477
PMCPMC4007438
OpenAlexW2115575348

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.