December 20, 2010
University of New England Pharmacology Professor Amy Davidoff, Ph.D., College of Osteopathic Medicine, is co-investigator on a recently funded grant from the Diabetes Australia Research Trust (DART) to continue her research on the relationship between heart failure and diabetes.
The research project, titled "A new link between altered glucose handling and impaired myocardial function in the diabetic heart," represents a collaborative effort between Dr. Davidoff and Rebecca Ritchie, Ph.D., of the Baker Heart Institute in Melbourne Australia. They will focus on the interaction of excess sugar inside the heart muscle and how it adversely affects heart function and leads to heart failure associated with diabetes.
Dr. Davidoff will be conducting the research at Dr. Ritchie's laboratory in Australia during a sabbatical beginning in spring semester 2011.
Dr. Ritchie's research program has access to several key components to explore the underlying causes and progression of heart failure with diabetes. Dr. Davidoff will be helping her host‚Äôs team develop specific skills relating to how to assess heart muscle cell mechanical function and explore intracellular signaling associated with abnormal sugar handling.
"Our research may ultimately facilitate the development of exciting new ways to treat diabetic heart disease, and hence increase survival in humans," Dr. Davidoff said.
Background on the Research
Diabetes mellitus is an independent risk factor for cardiovascular disease in both men and women, and the incidence of the disease is rapidly increasing.
To make matters worse, when cardiovascular disease surfaces in a patient with diabetes, they fare worse in terms of survival than a non-diabetic patient with comparable cardiovascular disease. Although this is partially explained by blood vessel disease, it has become increasingly apparent that markedly debilitating changes occur in the diabetic heart.
Diabetic heart disease is a distinct and common entity, characterized by cardiac dysfunction (impaired pumping). In particular, how the heart recovers from each heart beat in diabetic patients takes longer and is less efficient than people without diabetes; this impaired recovery is directly related to patient prognosis over the longer term.
Dr. Ritchie, an expert in heart failure resulting from high blood pressure, has previously shown that cardiac complications in the intact heart are similar in hypertrophic (enlarged) hearts as in diabetic hearts. She has also shown the ability of high glucose levels (hyperglycemia) to trigger the generation of toxic chemicals by the heart known as free radicals, which may be involved in these failing hearts.
Prof. Davidoff, an expert in the pathogenesis of heart failure due to diabetes, has shown that hyperglycemia adversely effects the electrical and mechanical functions of individual cardiac muscle cells (cardiomyocytes), and how excess glucose changes in the way the muscle cells regulate intracellular calcium.
Dr. Davidoff's laboratory has shown that hyperglycemia alone is sufficient to cause impairment in the ability of individual heart muscle cells to contract and relax, which likely explains much of the impairment of the intact heart's ability to pump and recover with each heart beat.
The two researchers will now investigate the biochemical mechanism by which high glucose and diabetes cause impairments in function of isolated myocytes, through abnormal glucose handling and whether these mechanisms actually trigger the generation of free radicals, and if they can be normalized by antioxidants.
"By better understanding the biochemical mechanism by which diabetes impairs the function of the heart, we can specifically target drug therapy to this."Prof. Davidoff explained. "Our combined expertise uniquely positions us to address these questions."