Amylin: new insight into pathogenesis, diagnosis, and prognosis of non-insulin-dependent diabetes-mellitus-related cardiomyopathy

Abstract Co-secretion with insulin, highly amyloidogenic human amylin is considered to contribute to the initiation and progression of diabetic heart complications, despite other situations such as hypertension and atherosclerosis. In response to insulin resistance, hyperinsulinemia, and consequently hyperamylinemia, is common in prediabetic patients, where highly concentrated amylin is prone to form amylin oligomers, which further assemble into fibrils and amyloids with high β-sheet content. The infusion and deposition of oligomeric amylin in myocytes cause a series of consequences, including cytosolic Ca2+ dysregulation, calmodulin activation, myocyte hypertrophy, and ventricular stiffness, eventually leading to heart failure. In this review, we present the latest reports of amylin-related heart complications, provide new insights, and state the underlying pathogenesis, diagnosis, possible treatment, and prevention of diabetic cardiomyopathy.