Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NF kappa B-Opa-1 Signaling Pathway

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dc.contributor.authorParra, Valentina
dc.contributor.authorVerdejo, Hugo E.
dc.contributor.authorIglewski, Myriam
dc.contributor.authordel Campo, Andrea
dc.contributor.authorTroncoso, Rodrigo
dc.contributor.authorJones, Deborah
dc.contributor.authorZhu, Yi
dc.contributor.authorKuzmicic, Jovan
dc.contributor.authorPennanen, Christian
dc.contributor.authorLopez Crisosto, Camila
dc.contributor.authorJana, Fabian
dc.contributor.authorFerreira, Jorge
dc.contributor.authorNoguera, Eduard
dc.contributor.authorChiong, Mario
dc.contributor.authorBernlohr, David A.
dc.contributor.authorKlip, Amira
dc.contributor.authorHill, Joseph A.
dc.contributor.authorRothermel, Beverly A.
dc.contributor.authorAbel, Evan Dale
dc.contributor.authorZorzano, Antonio
dc.contributor.authorLavandero, Sergio
dc.date.accessioned2024-01-10T13:44:28Z
dc.date.available2024-01-10T13:44:28Z
dc.date.issued2014
dc.description.abstractInsulin 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-NFB 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-NFB pathway.
dc.description.funderBicentennial Program, Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
dc.description.funderCONICYT
dc.description.funderAmerican Heart Association
dc.description.funderAmerican Heart Association-Jon Holden DeHaan Foundation
dc.description.funderNational Institutes of Health
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico
dc.description.funderFondo de Financiamiento de Centros de Investigacion en Areas Prioritarias
dc.description.funderGeneralitat de Catalunya, CIBERDEM (Instituto de Salud Carlos III)
dc.description.funderMinisterio de Educacion y Ciencia
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.description.funderNATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
dc.fechaingreso.objetodigital2024-05-09
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.2337/db13-0340
dc.identifier.eissn1939-327X
dc.identifier.issn0012-1797
dc.identifier.pubmedidMEDLINE:24009260
dc.identifier.urihttps://doi.org/10.2337/db13-0340
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78896
dc.identifier.wosidWOS:000328680400016
dc.information.autorucFacultad de Medicina; Verdejo Pinochet, Hugo Eduardo; S/I; 1001175
dc.issue.numero1
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final88
dc.pagina.inicio75
dc.publisherAMER DIABETES ASSOC
dc.revistaDIABETES
dc.rightsregistro bibliográfico
dc.subjectNF-KAPPA-B
dc.subjectDOWN-REGULATION
dc.subjectGTPASE OPA1
dc.subjectMOUSE MODEL
dc.subjectMUSCLE
dc.subjectHEART
dc.subjectDISEASE
dc.subjectMETABOLISM
dc.subjectACTIVATION
dc.subjectMECHANISMS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInsulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NF kappa B-Opa-1 Signaling Pathway
dc.typeartículo
dc.volumen63
sipa.codpersvinculados1001175
sipa.indexWOS
sipa.indexPubmed
sipa.trazabilidadCarga SIPA;09-01-2024
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