Obesity is a serious public health problem affecting one third of Americans. Obesity is a major risk factor for type II diabetes. Obesity results from an imbalance between energy intake and energy expenditure, which is controlled by the interaction between peripheral hormonal signals and the central nervous system. The proposed studies focuses on the underlying mechanism by which fat-specific overexpression of an Disulfide-bond A oxidoreductase-like protein enhances resistance to diet-induced obesity in mice, which will increase our understanding of the underlying metabolitc abnormalities of obesity.
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 covers the areas of adiponectin multimerization and its effects on fat and glucose metabolism. Adiponectin has been well established as an insulin sensitizer. numerous studies have demonstrated a significant correlation between adiponectin multimerization and its insulin sensitizing effects. Thus, enhancing multimerization of endogenous adiponectin may be a promising and effective therapeutic strategy. Our proposed research focuses on the role of DsbA-L, a protein we have recently identified to promote adiponectin multimerization in 3T3-L1 adipocytes. The proposed study will address the question as to whether enhancing adiponectin multimerization could be an effective approach for preventing diet-induced obesity and insulin resistance in vivo.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
The anti-inflammatory, anti-diabetic, and anti-atherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high levels of this adipokine in the serum. On the other hand, numerous studies suggest that enhancing adiponectin multimerization could be an effective approach to improve insulin sensitivity. Our study will determine whether increasing adiponectin multimers improves insulin resistance in animal models of obesity, which may lead to the development of new therapeutic treatment for insulin resistance and type 2 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 have been involved in diabetes research throughout my career. I received an ADA career development award during my early career development that jump-started my career in diabetes research. I have been a member of the ADA since I became an independent researcher in 1996 and participated in numerous research grant review meetings, ADA meeting abstract reviews and other activities. Diabetes research has been particularly important to me not only because this serious disease affects millions of people worldwide, but also because the lack of sufficient knowledge to develop effective therapeutic treatment for the cure and prevention of diabetes. The current award will allow us to determine whether enhancing adiponectin multimerization could be an effective approach to improve obesity, insulin resistance and type 2 diabetes.
In what direction do you see the future of diabetes research going?
I anticipate more and more anti-obesity and insulin resistance drug targets will be identified. I also anticipate an increase in translational research: from bench to bedside and from bedside to clinical practice.