Evidence map›Paper›PMID 24009260›Full record

ArticleDiabetes2014

Insulin stimulates mitochondrial fusion and function in cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 signaling pathway.

Valentina Parra, Hugo E Verdejo, Myriam Iglewski, Andrea Del Campo, Rodrigo Troncoso, Deborah Jones, Yi Zhu, Jovan Kuzmicic, Christian Pennanen, Camila Lopez-Crisosto and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed
7.5field-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

133 citing papers in PubMed, 219 citations in OpenAlex.

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73 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

21 authors at 7 institutions in 4 countries.

Valentina ParraAdvanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Hugo E Verdejo
Myriam Iglewski
Andrea Del Campo
Rodrigo Troncoso
Deborah Jones
Yi Zhu
Jovan Kuzmicic
Christian Pennanen
Camila Lopez-Crisosto
Fabián Jaña
Jorge Ferreira
Eduard Noguera
Mario Chiong
David A Bernlohr
Amira Klip
Joseph A Hill
Beverly A Rothermel
Evan Dale Abel
Antonio Zorzano
Sergio Lavandero
University of Chile · CLAdvanced Center for Chronic Diseases · CLThe University of Texas Southwestern Medical Center · USUniversity of Utah · USInstitute for Research in Biomedicine · ESHospital for Sick Children · CAUniversity of Minnesota · US

Funding

Obesity and Energy Metabolism CoreP30DK050456 · NIDDK · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BERNLOHR, DAVID A · 1995 to 2015
$17.0M
Modulating Calcineurin Signaling Pathways in MuscleR01HL072016 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHERMEL, BEVERLY A · 2003 to 2012
$3.7M
HDAC Inhibition in Cardiac Hypertrophy and FailureR01HL080144 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2007 to 2011
$2.0M
Modeling Diabetic Cardiomyopathy and Microangiopathy U01HL087947 · NHLBI · UNIVERSITY OF UTAH · PI ABEL, E DALE · 2006 to 2010
$1.8M
Calcineurin-Mediated Regulation of Cardiac Ca2+ ChannelR01HL075173 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2005 to 2009
$1.7M
Mitochondrial Dysfunction and Adipose Insulin ResistanceR01DK084669 · NIDDK · UNIVERSITY OF MINNESOTA · PI BERNLOHR, DAVID A · 2010 to 2014
$1.6M
Foxo: Negative Regulator of Cardiac HypertrophyR01HL090842 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HILL, JOSEPH A · 2009 to 2012
$1.6M
Calcineurin's role in circadian regulation of cardiac function and remodelingR01HL097768 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI ROTHERMEL, BEVERLY A · 2009 to 2012
$1.6M
Insulin Signaling and the Heart in DiabetesR01DK092065 · NIDDK · UNIVERSITY OF UTAH · PI ABEL, E DALE · 2010 to 2011
$649k
NHLBI NIH HHS HL-072016NHLBI NIH HHS HL-075173NHLBI NIH HHS HL-080144NHLBI NIH HHS HL-087947NHLBI NIH HHS HL-090842NHLBI NIH HHS HL-097768NHLBI NIH HHS R01 HL072016NHLBI NIH HHS R01 HL075173NHLBI NIH HHS R01 HL080144NHLBI NIH HHS R01 HL090842NHLBI NIH HHS R01 HL097768NHLBI NIH HHS U01 HL087947NIDDK NIH HHS DK-092065NIDDK NIH HHS P30 DK050456NIDDK NIH HHS R01 DK084669NIDDK NIH HHS R01 DK092065
6 · The paper itself

Abstract

Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo. Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway.

Indexed as

AnimalsCell LineCells, CulturedGTP PhosphohydrolasesInsulinMiceMice, TransgenicMitochondriaMitochondrial DynamicsMuscle, SkeletalMyocytes, CardiacNF-kappa BProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionGTP PhosphohydrolasesInsulinmTOR protein, ratNF-kappa BOpa1 protein, ratProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinases

Identifiers

PMID24009260
PMCPMC3868041
OpenAlexW2154726349

What OpenQuestion holds

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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.