Jiang, Zhen Yue, PhD
Role of PPC2D in Exercise-Regulated Glucose Metabolism
General Research Subject: Both Type 1 And Type 2 Diabetes
Focus: Exercise\Animal, Insulin Action, Insulin Action\Glucose Transport, Insulin Action\Signal Transduction
Type of Grant: Minority Undergraduate Internship
Project Start Date: January 1, 2013
Project End Date: December 31, 2013
Diabetes is a serious disease, marked by higher than normal levels of glucose (sugar) in the blood. The normal blood glucose level in humans is about 4 mM (4 mmol/L or 72 mg/dL, i.e. milligrams/deciliter). The body naturally tightly regulates blood glucose levels as a part of metabolic homeostasis. Human metabolic homeostasis is mainly controlled by insulin. Insulin controls blood glucose levels partially by moving glucose transporter GLUT4 in muscle and adipose tissue from peri-nuclear area to cell surface and promotes muscle cells and adipocytes glucose uptake from blood stream. Other cellular molecules, like AMPK and CaMKII also regulate blood glucose levels. PPC2D is a recently identified C2-domain containing phosphor-protein that has been activated by CaMKII and involved in insulin induced GLUT4 translocation.
This internship project is to study the exercise's effect on PPC2D protein expression in muscles of wild-type (WT) mice and to compare AMPK and CaMKII phosphorylation changes in muscles of WT and PPC2D knock-out mice before and after exercise. Mice will be subjected to physical exercise for 30 minutes per day, three days per week using a treadmill for 4 weeks. Mouse blood glucose levels, body weight, body composition, PPC2 protein expression and AMPK and CaMKII phosphorylation will be measured before and after exercise. These studies will offer insight for understanding the physiological roles of PPC2D in exercise-regulated glucose metabolism and the molecular mechanisms by which exercise may improve diabetes.
Mentor: Zhen Yue Jiang
Undergraduate: Karla Candelaria
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and curing diabetes?
Physical exercise is an important therapeutic approach for the treatment of type II diabetes. Exercise does that by regulating glucose (sugar) utilization and by mobilizing glucose transporter GLUT4 from inside to the surface of the cells. This project is aimed at understanding the mechanism by which exercise regulates sugar utilization in our cells We identified a new protein PPC2D that is required for insulin-regulated glucose transport and GLUT4 movement from inside to the surface of the cells. This project is designed to determine if PPC2D is required in the regulation of glucose transport and glucose metabolism induced by physical exercise in mice. We will compare the effects of exercise on glucose metabolism in mice lacking PPC2D and mice with normal PPC2D. This study could provide important information how glucose metabolism is regulated by exercise. Since PPC2D is a protein highly regulated in obesity, it might be a potential therapeutic target for diabetes and its complications.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
It is well-established that exercise is important in regulating blood sugar (glucose) levels by stimulating glucose transport into the fat and muscle cells for metabolism. Blood glucose levels are elevated in both type I diabetes (insulin deficiency) and type II diabetes (insulin resistance). The elevation of blood sugar is a major factor contributing to the development of diabetes-associated complications.
The goal of this project is to understand how exercise regulates glucose transport and utilization. In particular, we are studying the role of a new protein molecule PPC2D in exercise-stimulated glucose metabolism. Insights from these studies may help us to identify potential steps and new molecules involved in the regulation of glucose utilization. Therefore, the outcome of this project might help to identify new drug target(s) for intervening glucose transport and treatment of diabetes and its complications.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
Diabetes is one of the most serious health problems affecting more than 171 million people in 2008 worldwide and this is expected to increase to 366 million by 2030. I have been involved in diabetes-related research for more than a decade. It is my passion to understand how exercise and insulin regulate glucose transport and utilization. Previously, we confirmed that insulin signaling via protein kinase Akt2 pathway is important for glucose transport.
With the support of a Junior Faculty Award from the American Diabetes Association, I applied quantitative proteomic and functional screening approaches to identify an isoform of C2 domain-containing phosphoprotein PPC2D that is required for insulin-stimulated glucose transport and GLUT4 translocation. The support from the recent Basic Research Award and this new MUI training program from the American Diabetes Association will enable my lab to further study how PPC2D regulates glucose metabolism in adipocytes and muscle cells in response to insulin and physical exercise.
In what direction do you see the future of diabetes research going?
Both exercise and insulin are important for maintaining glucose homeostasis in our body. Impaired insulin action and lack of physical activity are both involved in the development of diabetes. I believe that studies related to identifying new factors that are required for glucose metabolism and regulated by exercise are important for diabetes research.
My current project relates to this area. Applications of advanced techniques, such as quantitative proteomics, lipidomics, genomics, and quantitative microscopy methods, will also help fundamental discoveries in diabetes-related research. These areas of research are critical for the discovery of new therapeutic targets and drugs for diabetes. As we continue to gain insights into the molecular mechanism by which insulin and exercise stimulate glucose transport and metabolism, we are identifying potential intervene approaches to improve glucose utilization and therefore, new methods for the treatment of diabetes and its complications.
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