Abstract 11116: Hyperamylinemia Increases the Cardiac Risk in Pre-diabetes
Amylin is a peptide known to form amyloids that injure pancreatic cells in type-2 diabetes (T2D) patients. We have recently shown that amylin also affects the heart. Using a T2D rat model transgenic for human amylin (HIP rat), we found that cardiac deposition of amylin accelerates heart failure by altering sarcolemmal processes. Hence, we hypothesized that i) amylin buildup at the sarcolemma is promoted by hyperamylinemia, a common condition in obesity and pre-diabetic insulin resistance, and ii) limiting cardiac deposition of amylin is cardioprotective.
Here, we used an amylin antibody to assess the amylin level in cardiac myocyte lysates from two groups of pre-diabetic patients, including obese (body mass index, BMI, ≥30) that developed T2D within 1 year post-transplantation (O-HF; N=5) and obese without heart failure (O-NF; N=6). Failing hearts from non-obese non-diabetic patients (L-HF; N=5) and hearts from non-obese (BMI<30) patients without heart failure (L-NF; N=4) served as controls. The oligomerized amylin level was ~10 times higher in cardiac myocytes from O-HF patients compared to those in control L-NF and L-HF groups. Increased incorporation of amylin in myocytes was observed even in OB-NF subjects compared to that in L-NF patients (by ~300%) showing an early buildup of amylin at the sarcolemma. The results suggested that the increased interaction of oligomerized amylin with cardiac cells in humans is linked with the development of heart disease.
Next, we drastically reduced amylin attachment to the sarcolemma in HIP rats by pharmacologically elevating the blood level of pro-fibrinolytic eicosanoids. Animals in the treated group displayed reduced cardiac hypertrophy and dilation. Possible cardioprotective mechanisms include limiting amylin-induced cardiac oxidative stress and myocyte Ca2+ cycling alteration. The results suggest that blocking cardiac amylin accumulation protects the heart in pre-diabetes.
- © 2013 by American Heart Association, Inc.