Evidence map›Paper›PMID 20404042›Full record

ArticleExperimental biology and medicine (Maywood, N.J.)2010

Insulin inhibits human erythrocyte cAMP accumulation and ATP release: role of phosphodiesterase 3 and phosphoinositide 3-kinase.

Madelyn S Hanson, Alan H Stephenson, Elizabeth A Bowles, Randy S Sprague

Open access · greenAbstract read
In one paragraph

Article in Experimental biology and medicine (Maywood, N.J.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.4field-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

20 citing papers in PubMed, 38 citations in OpenAlex.

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  11. Synergistic effects of C-peptide and insulin on low O2-induced ATP release from human erythrocytes.American journal of physiology. Regulatory, integrative and comparative physiology · 2013
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  19. Defects in oxygen supply to skeletal muscle of prediabetic ZDF rats.American journal of physiology. Heart and circulatory physiology · 2010
    Article
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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.

Madelyn S HansonDepartment of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, MO 63104, USA. mhanson@mcw.edu
Alan H Stephenson
Elizabeth A Bowles
Randy S Sprague
Saint Louis University · US

Funding

RESEARCH TRAINING IN TRANSFUSION SCIENCET32HL007209 · NHLBI · VERSITI WISCONSIN, INC. · PI WHITE, II, GILBERT C. · 1985 to 2019
$2.9M
MECHANISMS OF DEFORMATION-INDUCED ATP RELEASE FROM RBCSR01HL064180 · NHLBI · SAINT LOUIS UNIVERSITY · PI SPRAGUE, RANDY · 2000 to 2007
$2.3M
Microvascular O2 Delivery: Impact of Erythrocyte-Released ATPR33HL089094 · NHLBI · SAINT LOUIS UNIVERSITY · PI ELLSWORTH, MARY L · 2007 to 2009
$1.6M
NHLBI NIH HHS HL-64180NHLBI NIH HHS HL-89094NHLBI NIH HHS R01 HL064180NHLBI NIH HHS R33 HL089094NHLBI NIH HHS T32 HL007209
6 · The paper itself

Abstract

In non-erythroid cells, insulin stimulates a signal transduction pathway that results in the activation of phosphoinositide 3-kinase (PI3K) and subsequent phosphorylation of phosphodiesterase 3 (PDE3). Erythrocytes possess insulin receptors, PI3K and PDE3B. These cells release adenosine triphosphate (ATP) when exposed to reduced O(2) tension via a signaling pathway that requires activation of the G protein, Gi, as well as increases in cAMP. Although insulin inhibits ATP release from human erythrocytes in response to Gi activation by mastoparan 7 (Mas 7), no effect on cAMP was described. Here, we investigated the hypothesis that insulin activates PDE3 in human erythrocytes via a PI3K-mediated mechanism resulting in cAMP hydrolysis and inhibition of ATP release. Incubation of human erythrocytes with Mas 7 resulted in a 62 +/- 7% increase in cAMP (n = 9, P < 0.05) and a 306 +/- 69% increase in ATP release (n = 9, P < 0.05), both of which were attenuated by pre-treatment with insulin. Selective inhibitors of PDE3 (cilostazol) or PI3K (LY294002) rescued these effects of insulin. These results support the hypothesis that insulin activates PDE3 in erythrocytes via a PI3K-dependent mechanism. Once activated, PDE3 limits Mas 7-induced increases in intracellular cAMP. This effect of insulin leads, ultimately, to decreased ATP release in response to Mas 7. Activation of Gi is required for reduced O(2) tension-induced ATP release from erythrocytes and this ATP release has been shown to participate in the matching of O(2) supply with demand in skeletal muscle. Thus, pathological increases in circulating insulin could, via activation of PDE3 in erythrocytes, inhibit ATP release from these cells, depriving the peripheral circulation of one mechanism that could aid in the regulation of the delivery of O(2) to meet tissue metabolic need.

Indexed as

Adenosine TriphosphateAdultChromonesCilostazolCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 3Enzyme InhibitorsErythrocytesFemaleGTP-Binding Protein alpha Subunits, Gi-GoHumansInsulinIntercellular Signaling Peptides and ProteinsIn Vitro TechniquesMaleMiddle Aged2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneAdenosine TriphosphateChromonesCilostazolCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 3Enzyme InhibitorsGTP-Binding Protein alpha Subunits, Gi-GoInsulinIntercellular Signaling Peptides and ProteinsMas7 protein, syntheticMorpholinesOxygenPeptidesPhosphatidylinositol 3-KinasesPhosphodiesterase 3 InhibitorsPhosphoinositide-3 Kinase InhibitorsTetrazoles

Identifiers

PMID20404042
PMCPMC2892266
OpenAlexW2058126361

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.