Long-standing hyperglycemia-induced activation of PKC, through predominately a de novo synthesis of DAG, has been confirmed to thicken basement membrane, reduce blood flow and deposit ECM in the heart from both diabetic rodents and patients, which renders the development of DCM from cardiac inflammation, hypertrophy, fibrosis and diastolic dysfunction to heart failure (62, 66–69). This evidence concerns the gene PRRT2 and familial dilated cardiomyopathy.