Yan, Zhen , MD, PhD
Mitochondrial permeability transition and mitophagy in type 2 diabetes
General Research Subject: Type 2 Diabetes
Focus: Integrated Physiology\Insulin Resistance, Integrated Physiology\Muscle
Type of Grant: Basic Science
Project Start Date: January 1, 2011
Project End Date: December 31, 2013
Diabetes Type: Type 2 diabetes
Adult-onset (type 2) diabetes is a detrimental chronic disease that has recently increased dramatically and globally. The proposed research focuses on the importance of the maintenance of the powerhouses of our body, mitochondria, in the development of this disease. Animal models that mimic the conditions of human patients will be used to obtain the scientific evidence. The expected findings will significantly improve our understanding of the disease and foster effective therapies. Because the findings will be highly relevant to the situation in human patients of type 2 diabetes, our findings will be directly beneficial to millions of Americans. The findings will be relevant to the mission of American Diabetes Association and be broadly interesting to researchers in the area of metabolism.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Adult-onset (type 2) diabetes is a detrimental chronic disease that has recently increased dramatically worldwide. As an important and initial problem of the disease, skeletal muscles become insensitive to the hormone insulin possibly due to abnormal function of the powerhouses, mitochondria. The proposed research focuses on the importance of mitochondrial maintenance in the development of this disease. Specifically, we will use mouse genetic models under the condition that mimics human patients to assess the roles of two potentially critical steps in mitochondrial maintenance: mitochondrial damage and clearance. The expected findings will significantly improve our understanding of the disease and foster effective therapies. Because the findings will be highly relevant to human patients of type 2 diabetes, our findings will be directly beneficial to millions of Americans.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Accumulation of damaged mitochondria in cells in our body is associated with many chronic diseases, particularly in type 2 diabetes, and may play an important role in the onset and prognosis; however, the reasons behind it are not clear. Based on our preliminary data, we speculated that a disrupted balance between mitochondrial damage and removal is underlying the accumulation of damaged mitochondria in skeletal muscle under a diabetic condition. We plan to mutate the genes that might be essential for these two steps in mice to obtain direct evidence for this hypothesis. These findings will likely provide valuable information for future research and facilitate therapeutic interventions to tackle this problem. Correction of the mitochondrial defects may cure or improve the disease conditions.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Trained as a physician scientist, I have seen many patients suffering from adult-onset (type 2) diabetes and its complications. I have dedicated my research to help develop effective preventive and therapeutic strategies for this detrimental disease. Having received proper training and generous support from numerous scientists in the field for the past 20 years, I am poised to make a meaningful contribution to the cause of conquering diabetes. This award will give me the best opportunity to realize this long-term personal dream.
In what direction do you see the future of diabetes research going?
The direction that I would like to see for future diabetes research is to promote an environment for training scientists in both basic science and clinical medicine, and for innovative research on the fundamental mechanisms of type 2 diabetes. In particular, I think that integrative animal and human research that focus on the environment-gene interaction (epigenetic regulation) converging on the functional regulation of key subcellular organelles, such as mitochondria, will be critical in providing instrumental information for the prevention and cure of type 2 diabetes.
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