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Authordc.contributor.authorBattiprolu, Pavan K. 
Authordc.contributor.authorHojayev, Berdymammet es_CL
Authordc.contributor.authorJiang, Nan es_CL
Authordc.contributor.authorWang, Zhao V. es_CL
Authordc.contributor.authorLuo, Xiang es_CL
Authordc.contributor.authorIglewski, Myriam es_CL
Authordc.contributor.authorShelton, John M. es_CL
Authordc.contributor.authorGerard, Robert D. es_CL
Authordc.contributor.authorRothermel, Beverly A. es_CL
Authordc.contributor.authorGillette, Thomas G. es_CL
Authordc.contributor.authorLavandero González, Sergioes_CL
Authordc.contributor.authorHill, Joseph A. es_CL
Admission datedc.date.accessioned2012-05-23T21:33:37Z
Available datedc.date.available2012-05-23T21:33:37Z
Publication datedc.date.issued2012-03
Cita de ítemdc.identifier.citationJOURNAL OF CLINICAL INVESTIGATION Volume: 122 Issue: 3 Pages: 1109-1118 Published: MAR 2012es_CL
Identifierdc.identifier.issn0021-9738
Identifierdc.identifier.otherDOI: 10.1172/JCI60329
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/121629
Abstractdc.description.abstractThe leading cause of death in diabetic patients is cardiovascular disease; diabetic cardiomyopathy is typified by alterations in cardiac morphology and function, independent of hypertension or coronary disease. However, the molecular mechanism that links diabetes to cardiomyopathy is incompletely understood. Insulin resistance is a hallmark feature of diabetes, and the FoxO family of transcription factors, which regulate cell size, viability, and metabolism, are established targets of insulin and growth factor signaling. Here, we set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy. We found that FoxO proteins were persistently activated in cardiac tissue in mice with diabetes induced either genetically or by high-fat diet (HFD). FoxO activity was critically linked with development of cardiomyopathy: cardiomyocyte-specific deletion of FoxO1 rescued HFD-induced declines in cardiac function and preserved cardiomyocyte insulin responsiveness. FoxO1-depleted cells displayed a shift in their metabolic substrate usage, from free fatty acids to glucose, associated with decreased accumulation of lipids in the heart. Furthermore, we found that FoxO1-dependent downregulation of IRS1 resulted in blunted Akt signaling and insulin resistance. Together, these data suggest that activation of FoxO1 is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease.es_CL
Patrocinadordc.description.sponsorshipNIH HL-075173 HL-080144 HL-090842 HL-072016 HL 097768 American Heart Association 0640084N 0655202Y American Diabetes Association 7-08-MN-21-ADA American Heart Association-Jon Holden DeHaan Foundation 0970518N Fondo Nacional de Desarrollo Cientifico y Tecnologico, Chile FONDECYT 1120212 FONDAP 1500006es_CL
Lenguagedc.language.isoenes_CL
Publisherdc.publisherAMER SOC CLINICAL INVESTIGATION INCes_CL
Keywordsdc.subjectFATTY-ACID UTILIZATIONes_CL
Títulodc.titleMetabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in micees_CL
Document typedc.typeArtículo de revista


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