Yi, Zhengping , PhD
Effect of Exercise on Human Skeletal Muscle Tyrosine Phosphoproteome
General Research Subject: Insulin Resistance Pre Diabetes
Focus: Exercise, Exercise\Human, Insulin Action, Insulin Action\Insulin Resistance, Insulin Action\Signal Transduction
Type of Grant: Translational Science
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Insulin resistance is a primary contributor to the development of obesity-related diseases, such as type 2 diabetes. Exercise is known to greatly improve insulin resistance, and it is clear that a physically active lifestyle can enhance human health. However, the mechanisms underlying the exercise-induced improvements in insulin resistance remain largely unknown. Tyrosine phosphorylation is a reversible process that is very important in regulating many cellular events, including insulin action. One possible reason why people develop insulin resistance and type 2 diabetes is that tyrosine phosphorylation is not working properly in their muscles.
The hypothesis of this proposal is that exercise improves insulin sensitivity by increasing new, as yet unidentified, tyrosine phosphorylation events within skeletal muscle. Proteomics offers the ability to quantify hundreds of protein tyrosine phosphorylation sites simultaneously, providing a global picture of tyrosine phosphorylation.
The proposed studies will be the first to examine the effects of exercise on the overall tyrosine phosphorylation in muscle from human volunteers by state-of-the-art proteomics technologies. We will study tyrosine phosphorylation events in muscles from a group of obese adults who live physically active lifestyles and a separate group of obese adults who are normally very inactive. The overall goal is to understand how exercise improves insulin action and to provide novel targets for prevention and treatment of type 2 diabetes. The findings from the projects proposed in this application may be used to optimize therapeutic and preventative treatment programs, as well as in the design of drugs targeted at improving human health.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
My project addresses the effects of exercise on insulin resistance in obese adults who are at risk for developing Type 2 diabetes.
Insulin resistance is a primary contributor to the development of obesity-related diseases, such as type 2 diabetes. Exercise is known to greatly improve insulin resistance, and it is clear that a physically active lifestyle can enhance human health. However, the mechanisms underlying the exercise-induced improvements in insulin resistance remain largely unknown. The goal of the project is to identify mechanisms responsible for improved insulin action by exercise. Findings from our study will expand our understanding for HOW exercise improves insulin resistance, and importantly our findings will provide novel targets for preventing and treating type 2 diabetes.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
Although exercise is known to improve insulin resistance and thereby reverse some key symptoms of diabetes -- it is very surprising that we really do not have a complete understanding for HOW exercise works to do this. Our project focuses on the effects of very specific biological events that may occur in muscle (i.e., changes in tyrosine phosphorylation state of some key proteins in muscle) that may help explain how exercise improves insulin resistance. We anticipate that the findings from this project will identify new targets that can be used in the development of drugs aimed at improving metabolic health, as well as help us to optimize therapeutic and preventative treatment programs for 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?
Insulin resistance, diabetes and their complications affect more than 100 million individuals in the US and lead to more than 300 billion dollars in health care costs each year. Although many research groups are focused on understand the cause of diabetes, only a few are using the state-of-the-art technologies developed in my laboratory. The idea that my work is both interesting from a basic science perspective and may have a global impact on the treatment and prevention of diabetes is very important to me. I would love to make a contribution to the prevention and treatment of diabetics.
This Translational Science Research Award will be the 3rd extramural grant that I serve as the principle investigator and it is a logical extension of my current ADA clinical/translational award, which will expire on 06/30/2013. This new award will enable me to continue the challenging in vivo human studies regarding differential phosphoproteome in obesity and insulin resistance, advancing the field of type 2 diabetes research and care.
In what direction do you see the future of diabetes research going?
The future of diabetes research will involve more collaborative efforts from a variety of scientific fields, such as clinical studies, physiology, biology, genomics, proteomics, metabolomics, bioinformatics, and statistics. It will also involve both hypothesis-testing projects and hypothesis-generating studies. Importantly, a primary overall objective of these collaborative efforts will be to translate information acquired in clinical and laboratory experiments (like those in the projects funded by this grant) into REAL therapeutic and preventative treatments for people who suffer from type 2 diabetes, and/or those who at risk for developing the disease.
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