P36 Aldosterone protects the insulin-activated AKT pathway in heart of diabetic type 2 mice

Introduction The pathogenesis of diabetic cardiomyopathy is not fully elucidated. Numerous factors may contribute to the development of heart failure in a diabetic context, including the scarcity of microvasculature and neurohumoral dysregulation, particularly the renin-angiotensin-aldosterone-system. We have previously shown that a modest increase of intracardiac aldosterone prevents the development of cardiomyopathy in mice with type 1 diabetes, possibly through a prevention of cardiac capillary dropout (Messaoudi et al, Faseb J 2009). This study aimed to determine the pathophysiological effects and to study transduction pathways of insulin in the case of a cardiac hyperaldosteronism with or without type 2 diabetes (T2D). Materiels et methodes 3 week-old mice overexpressing aldosterone synthase (AS), n = 9, and their wild-type (WT) littermates n = 5 were fed a high fat, high sucrose diet (HFHSD : 41 % fat, 43 % carbohydrate) or a standard diet ad libitum . After 4 months of diet, glucose and insulin tolerance tests were performed. Echocardiography was done, mice were sacrificed and tissue samples were used for RT-PCR, for immunoblotting and histological analyses. In addition, to analyze the signaling pathways dependent of the insulin receptor and insulin growth factor receptor, some of these mice (n = 5 for each group) received a dose of insulin (1 UI/kg body weight) 30 minutes before the sacrifice (Shimizu et al, JCI 2010). Resultats After 4 months of HFHSD, both WT-D and AS-D mice had hyperglycemia (+55 %, 56 %, P  Conclusion The results indicate that in mice developing T2D the AKT signaling pathway in heart could be stimulated by insulin only when cardiac hyperaldosteronism was present. This aldosterone-dependent activation of the AKT pathway might play a role in the induction of VEGFa in heart.