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Activation of insulin signaling prior to IPC abolishes cardioprotection in vivo

Grant number: 14/11638-9
Support type:Scholarships abroad - Research
Effective date (Start): September 01, 2014
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:Janaina Paulini Aguiar
Grantee:Janaina Paulini Aguiar
Host: Sihem Boudina
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Utah (U), United States  


Vogt and colleagues were among the first to show that insulin conferred cardioprotection in a porcine model of myocardial infarction via PI3K/Akt pathway, a finding that was further confirmed in ex vivo animal models of I/R. It is largely accepted that Akt activation by phosphorylation is strongly implicated in the cardioprotective response to I/R and that this signaling cascade leads to inhibition of mitochondrial permeability transition pore opening, which then reduce the necrotic effects of reperfusion. In contrast to the well-known cardioptotective effect of insulin against I/R, no studies have examined the effect of insulin on cardioprotection by IPC. Studies in my laboratory demonstrated for the first time that while insulin alone protected against I/R, it is combination with IPC abolished cardioprotection in Langendorff-perfused mouse heart via Akt-dependent mechanisms. Furthermore, recent evidence suggests that loss of protection by ischemic pre or post-conditioning is associated with activation of insulin signaling to Akt. Our recent studies using this preparation clearly demonstrated that insulin was detrimental for cardioprotection by IPC but whether this effect is also occurring in vivo has not been explored. In addition, we would like to investigate whether the detrimental effect of insulin on IPC is acute or requires a long-term exposure to this hormone. Therefore, this aim is designed to assess the efficacy of IPC against myocardial infarction during an acute or a long-term exposure to insulin in vivo. (AU)