Fig. 1.

Molecular mechanisms in cardiac insulin resistance via overnutrition and impaired insulin signaling leading to repetitive intermittent lack of energy in the early stage of cardiac dysfunction that is DD. The progression to remodeling processes including myocellular hypertrophy, altered titin, collagen and fibrosis metabolism, accumulation of triglycrides, and/or advanced glycemic end products and also the activation of the renin-angiotensin and sympathetic nervous system will lead to further myocardial cell damage and, potentially, to contractile dysfunction and/or heart failure. Ang II angiotensin II, ROS reactive oxygen species, ER endoplasmatic reticulum, eNOS endothelial nitric oxide synthase, SERCA sarcoplasmic endoplasmic reticulum Ca2+ - ATPase 2a, SR sarcoplasmatic reticulum (modified from [13])