Insulin/NFκB protects against ischemia-induced necrotic cardiomyocyte death
Author
dc.contributor.author
Díaz, Ariel
Author
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Humeres, Claudio
Author
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González, Verónica
Author
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Gómez, María Teresa
Author
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Montt, Natalia
Author
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Sánchez, Gina
Author
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Chiong Lay, Mario
Author
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García Nannig, Lorena
Admission date
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2018-12-20T15:13:07Z
Available date
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2018-12-20T15:13:07Z
Publication date
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2015
Cita de ítem
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Biochemical and Biophysical Research Communications, Volumen 467, Issue 2, 2015, Pages 451-457
Identifier
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10902104
Identifier
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0006291X
Identifier
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10.1016/j.bbrc.2015.09.171
Identifier
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https://repositorio.uchile.cl/handle/2250/158519
Abstract
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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.