mTOR/AKT/FOXO1 pathway is altered in the heart of the offspring from diabetic rats

DAIANA FORNES, SABRINA ROBERTI, HUGO SATO, ALICIA JAWERBAUM, ROMINA HIGA. ; DAIANA FORNES, SABRINA ROBERTI, HUGO SATO, ALICIA JAWERBAUM, ROMINA HIGA.

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Maternal diabetes programs cardiovascular alterations in the adult offspring, however very little is known about the mechanisms involved. Mammalian target of rapamycin (mTOR) is a key kinase involved in cellular growth, metabolism and survival, being part of complex 1 and 2 (mTORC1 and 2). Alterations in mTORC2-Akt signaling pathways are involved in cardiac failure mechanisms. Besides, FoxO1, a transcription factor whose activation is modulated by the mTORC2 pathway, participates in cellular oxidative homeostasis, metabolism and survival of cardiomyocites, and its overactivation is related with cardiac dysfunction in humans and experimental models of diabetes. FoxO1 activation can be inhibited by Akt phosphorylation that induces FoxO1 nuclear exportation. Our objective was to evaluate mTOR levels and Akt and FoxO1 phosphorylation status in the cardiac ventricle of male offspring from control and diabetic rats. Methodology: Pregestational mild diabetic rats were obtained by neonatal streptozotocin administration and were mated with healthy males. In the heart of adult offspring mTOR, Akt and FoxO1 levels and phosphorylation were evaluated by Western blot. Results: mTOR levels were found decreased in the heart of the offspring from diabetic rats (p