This indicates that the underlying cellular mechanism for upregulation of SERCA2a could be mediated by the PI3-kinase-Akt-SERCA2a signaling cascade, suggesting that subtle changes in Ca2+ regulation, which promote diastolic dysfunction prior to overt systolic dysfunction, may be common to early stages of type 2 diabetes involving insulin resistance[19,42]. This evidence concerns the gene AKT1 and Insulin resistance.