Li, Tiangang , PhD
Sortilin 1 in diabetic dyslipidemia
General Research Subject: Type 2 Diabetes
Focus: Diabetic Dyslipidemia, Integrated Physiology, Integrated Physiology\Fatty Acid Metabolism, Integrated Physiology\Liver
Type of Grant: Junior Faculty
Project Start Date: July 1, 2012
Project End Date: June 30, 2015
Obesity and diabetes are increasingly recognized as a health concern worldwide. Cardiovascular diseases, as a result of abnormal serum cholesterol and triglyceride levels, are prevalent among diabetic patients and are a major cause of death in diabetes. Unfortunately, the cause of such abnormal serum lipid levels in diabetes is still not clear. In our preliminary studies, we found that a liver protein called Sortilin1 was markedly decreased in the liver of mice with diabetes, and when we experimentally increased Sortilin 1 protein amount in the diabetic mouse livers, the serum cholesterol and triglyceride levels were returned to normal levels, which usually correlates with significant reduction in the risk of cardiovascular diseases. The purpose of the proposed research is to use cell line and mouse models to further study how increasing Sortilin 1 amount in the liver results in lower serum lipid. Results from these studies could improve our current understanding on the cause of abnormally elevated serum lipid in diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Diabetes is often associated with dyslipidemia with abnormal serum cholesterol and triglyceride levels. Diabetic dyslipidemia significantly increases the risk of cardiovascular disease, which is a major cause of morbidity and mortality in type-2 diabetes. This project is to investigate the role of a liver protein called Sortilin1 in regulating serum triglyceride levels. The questions we wish to answer are that what causes impaired liver Sortilin 1 function in diabetes and whether and how impaired Sortilin 1 function in the liver contributes to the development of abnormal serum triglyceride levels in diabetes. The results from this project could provide knowledge basis for future studies investigating if therapeutic interventions that improve Sortilin 1 function could be developed to improve dyslipidemia and reduce the risk of cardiovascular diseases among diabetic patients.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Cardiovascular disease is the leading cause of death in diabetes. Abnormal serum lipid levels are the major causes of increased risk of cardiovascular diseases among diabetic patients. However, preventing and managing diabetic dyslipidemia has been challenging due to the complex cause and multiple factors involved. This study could be deemed as part of the effort to improve current understanding on how lipid levels are controlled in normal and diseased conditions. Such knowledge obtained through basic research serves as important basis for future development of therapeutic strategies to treat lipid disorders that are closely associated 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 received my research training in the field of nuclear receptor regulation of lipid metabolism. My research interests have been in understanding the molecular links between bile acid metabolism and obesity/diabetes-associated metabolic disorders. Through my past research training, I have gained expertise in the area of lipid and glucose metabolism and gene regulation related to obesity and diabetes. The prestigious Junior Faculty Award from American Diabetes Association will facilitate my transition into an independent investigator and further allow me to conduct research that is aimed to improve current understanding on the pathogenesis of diabetes-related health problems.
In what direction do you see the future of diabetes research going?
As over-nutrition, obesity and insulin resistance are believed to be fundamental to various diabetes-related disorders and complications, promoting a healthy lifestyle among general population may be important to prevent metabolic disorders leading to the development of diabetes. In addition, future research that aims to improve understanding on the complex interactions between nutrition and metabolism and to develop strategies to improve metabolic homeostasis may be important in the advance of diabetes prevention and treatment.
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