title: Insulin/NFκB protects against ischemia-induced necrotic cardiomyocyte death.
abstract: In the heart, insulin controls key functions such as metabolism, muscle contraction and cell death. However, all studies have been focused on insulin action during reperfusion. Here we explore the cardioprotective action of this hormone during ischemia. Rat hearts were perfused ex vivo with an ischemia/reperfusion Langendorff model in absence or presence of insulin. Additionally, cultured rat cardiomyocytes were exposed to simulated ischemia in the absence or presence of insulin. Cytoprotective effects were measured by myocardial infarct size, trypan blue exclusion, released LDH and DNA fragmentation by flow cytometry. We found that insulin protected against cardiac ischemia ex vivo and in vitro. Moreover, insulin protected cardiomyocytes from simulated ischemia by reducing necrotic cell death. Protective effects of insulin were dependent of Akt and NFκB. These novel results show that insulin reduces ischemia-induced cardiomyocyte necrosis through an Akt/NF-κB dependent mechanism. These novel findings clarify the role of insulin during ischemia and further support its use in early GIK perfusion to treat myocardial infarction.
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Ariel
authors.initials: A
authors.lastname: Díaz
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Humeres
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: González
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Gómez
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Natalia
authors.initials: N
authors.lastname: Montt
authors.affiliation: Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Gina
authors.initials: G
authors.lastname: Sanchez
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
authors.affiliation: Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile. Electronic address: logarcia@ciq.uchile.cl.
authors.forename: Lorena
authors.initials: L
authors.lastname: García
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009924:Organ Culture Techniques; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D002316:Cardiotonic Agents; D007328:Insulin; D016328:NF-kappa B; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt
keywords: Cell death; Cell signaling; Heart; Insulin; Ischemia