Electrical Properties and Potential Arrhythmogenesis of the Insulin Resistance Heart

The prevalence of diabetes, metabolic syndrome and obesity are increasing at an alarming rate. This disturbing trend is partially the result of an epidemic increase in obesity, which is a major cause of type 2 diabetes. Insulin resistance is a major characteristic of obesity, type 2 diabetes, metabolic syndrome, and develops in multiple organs, including the heart. Daily consumption of food high in calories, especially sugar and fat has led to the obesity epidemic. This project is aimed to investigate the electrical substrate properties and arrhythmogenesis in prediabetic insulin resistance heart. We propose insulin resistance interacts with obesity, resulting to substrate for arrhythmia genesis and maintenance. Two insulin resistance models of rats will be created: (1) with obesity by high-cholesterol feeding and (2) without obesity by high-fructose feeding for 15 weeks. The electrical and structural properties of the heart will be studied. Then the hearts will be challenged by ischemia-reperfusion (I/R) injury. I/R injury-induced ventricular arrhythmia and underlying substrate changes will be studied. In vitro we will construct insulin resistance model in cultured myocytes and explore the signal pathways linking insulin resistance and arrhythmia. Finally we will utilize the National Health Insurance Research Database (NHIRD) released by the Taiwan National Health Research Institutes (NHRI) to explore potential underlying disease or prescribed medication as possible risk or protective factors of AF in patients of obesity, insulin resistance or type 2 diabetes. We expect this project will help understand the underlying mechanism of insulin resistance-related cardiac remodeling and arrhythmogenesis.

Project ID:PC10401-0243
External Project ID:NSC102-2628-B182-011-MY3