Semenkovich, Clay F., MD
Role of organ-specific de novo lipogenesis in regulation of glucose and lipid metabolism
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes, Integrated Physiology\Fatty Acid Metabolism
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2009
Project End Date: June 30, 2013
The most common cause of death in people with both type 1 and type 2 diabetes is heart disease. Unfortunately, even scrupulous control of blood sugar does not prevent heart problems, and while lowering cholesterol and decreasing blood pressure provide clear benefits, people with diabetes remain at risk for premature heart attacks and strokes despite these therapies. Most heart disease is caused by an abnormal accumulation of fats in blood vessels, a process known as atherosclerosis. This hardening of the arteries decreases blood flow to vital organs like the heart and brain. People with diabetes have abnormal fat metabolism in addition to abnormal glucose metabolism. We are committed to finding new ways to improve fat metabolism in diabetes and to training young scientists to pursue careers in diabetes research. This Mentor-Based Postdoctoral Fellowship will provide a supervised research experience in the setting of didactic instruction for fellows dedicated to seeking new knowledge to decrease the burden of cardiovascular disease in diabetes. The research experience includes involvement in one of several projects that deal with fat metabolism and cardiovascular disease in animal models, and each has the potential for translation to novel approaches in humans. As an example, we recently discovered in mice that the antimalarial drug chloroquine can reduce atherosclerosis, and this agent is now being tested in people with the metabolic syndrome, a prediabetes condition associated with atherosclerosis. Our goal is equip outstanding young scientists with the tools needed to improve the quality of life for people with diabetes.
Mentor: Clay Semenkovich, MD Postdoctoral Fellow: Mariko Johnson, MD
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project deals with how fat metabolism contributes to heart disease and stroke in people with diabetes. We approach this problem by using animal models to answer very focused questions, then attempt to identify ways that these answers in mice can be made relevant to diabetes in people. We have already employed this paradigm in an effort to prevent or treat the complications of diabetes. Using mice, we discovered that an antimalarial drug long available by prescription, chloroquine, can decrease blood vessel damage and lower blood glucose. We are now in the process of conducting a clinical trial in humans with the metabolic syndrome, a prediabetes condition, to determine if chloroquine can decrease blood vessel damage and improve the effectiveness of insulin.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
This project has the potential to discover new pathways that might provide new insight into why people with diabetes are at risk for heart disease and stroke. While I care for many people with diabetes and we work together to maintain scrupulous blood sugar control, this intervention has not been shown to be effective for preventing heart attacks and strokes in people with diabetes. By understanding how fat metabolism, which is known to be disrupted in diabetes, damages blood vessels, we hope to be able to provide leads for new therapies that may one day help everyone with diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
I was inspired to pursue a career in diabetes research by a high school English teacher. She took particular interest in me and provided direction and advice that was invaluable. Tragically, she died due to diabetes complications before I graduated from high school. However, I was one of the graduation speakers and paid tribute to her efforts.
I am also passionate about ensuring that others are committed to diabetes research. This award will continue to make it possible for me to identify and nurture the careers of young scientists who hope to improve the quality of life for people afflicted with diabetes.
In what direction do you see the future of diabetes research going?
I suspect that research will progress on two critical fronts. First, we need to better understand how currently available drugs impact the processes affected by diabetes. As an example, high doses of aspirin-like drugs improve specific pathways of inflammation and are now being used in clinical trials to treat diabetes. Second, we need to better understand how to motivate people to improve blood sugar control and follow medical regimens known to provide benefits in diabetes.
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