Fig. 4

Activation of cardiac mitochondrial AKT1 signaling protected against the development of diabetic cardiomyopathy. A The mito-caAKT1 construct containing a constitutively active AKT1 with a mitochondria localization sequence and 6x-His-tag. Phosphomimetic mutations were made at T308E and S473E. B Cardiac left ventricular septum thickness, posterior wall thickness and ventricular mass were analyzed by echocardiogram after 2 months of high fat chow and fructose water diet (HFFD) or normal chow diet, post TAM or CO injection. LV Mass is given as a relative percent of total heart mass (n = 6 (CO – normal chow), n = 7 (CO), n = 5(TAM); All p < 0.05). C Cardiac function was measured by echocardiogram after 5 months of HFFD or normal chow post TAM or CO injection. Left ventricular fractional shortening and ejection fraction were maintained in TAM-CAMCAKT mice (n = 7 (CO – normal chow), n = 10 (CO), n = 10 (TAM); All p < 0.05). D Expression of markers of heart failure: ANF, BNP, Col1, Col3, My7 measured by RT-qPCR after 5 months of HFFD post TAM or CO injection. Data are presented as relative fold change to CO-CAMCAKT (n = 8 (CO), n = 5(TAM); p < 0.05, < 0.01, < 0.0001, < 0.001, < 0.01). E Representative graph of mitochondrial respiration in CAMCAKT cardiac mitochondria after 2 months of HFFD post TAM or CO injection. F Basal respiration, stage 3 respiration, and proton leak in CAMCAKT mitochondria were calculated (n = 4; p < 0.05, < 0.01, < 0.05). G ATP levels in CAMCAKT mitochondria after 2 months of HFFD post TAM or CO injection. Data are presented as relative levels to CO-CAMCAKT (n = 4, p < 0.05)