Our research focuses on two major themes:
- The molecular mechanisms underlying the association of obesity and insulin resistance.
- Direct effects of adipokines on cardiomyocytes.
The significant physiological relevance of these studies is highlighted by the fact that obesity has become an epidemic in North America. Associated with this is an alarming increase in the incidence and a decrease in the age of onset of type 2 (insulin-resistant) diabetes. This means a vastly increased proportion of the population are susceptible to the myriad of complications associated with diabetes, including nephropathy, neuropathy, retinopathy, atherosclerosis, hypertension, heart failure and stroke. As a result, a major research initiative in this millennium will be a detailed understanding of the molecular basis for this observation. Type 2 diabetes is characterized by insulin resistance, the failure of peripheral tissues, including liver, muscle, and adipose tissue, to respond to physiologic doses of insulin, and a relative insufficiency of insulin production from pancreatic beta-cells in response to blood glucose levels. Obesity is a significant risk factor for the development of insulin resistance (80% of individuals with type 2 diabetes are obese) and it is believed that endocrine effects of hormones released by fat cells (adipokines) play an important role in the pathogenesis of insulin resistance.We are currently studying the role played by the adipokines leptin, resistin and adiponectin in glucose uptake and metabolism in skeletal muscle and investigating the signaling mechanisms responsible for effects of these adipokines. These studies are potentially exciting for the development of therapeutic approaches for the treatment of diabetes.
Obesity is also a major risk factor for development of heart failure which occurs when the heart is unable to pump sufficient blood to meet the demands of the body. Progression of heart failure is now commonly believed to result due to a complex interplay of detrimental effects (remodeling). The ability of leptin, the product of the obese (ob) gene, and other adipokines such as resistin and adiponectin to mediate direct effects on cardiac muscle may help explain the strong association between obesity and cardiovascular complications, including heart failure. Our work may aid the development of therapeutic strategies for the treatment of heart failure in obesity.