FIGURE 1.

In states of acute physiological stress, glucose is shunted into cardiomyocytes via upregulated GLUT‐1. Glucose is metabolized via glycolytic and non‐glycolytic pathways, generating reactive oxygen species that target intracellular proteins that activate apoptotic pathways. The positive inotropic effects of insulin are mediated by the activation of the insulin receptor PI3 K/Akt pathway, leading to increased activity of NCX (a sodium‐calcium exchanger) and intracellular calcium accumulation. Insulin also counteracts the negative effects of peroxynitrite by inhibiting apoptotic pathways in cardiomyocytes. Part of this effect is mediated through the increased expression of HSP70 and its preferential localization to the plasma membrane with dystrophin. Insulin receptor activation also leads to the translocation of hexokinase (HK) to the mitochondrial membrane, where it exerts its cardioprotective effects via three mechanisms: (a) suppressing the generation of ROS, (b) inhibiting the release of cytochrome C (CyC) into the cytosol, and (c) inhibiting the formation of mitochondrial pores