Liu, Meilian , PhD
The role of DsbA-L in regulating liver mitochondria function and insulin sensitivity
General Research Subject: Insulin Resistance Pre Diabetes
Focus: Insulin Action\Insulin Resistance, Insulin Action\Metabolism, Integrated Physiology\Liver
Type of Grant: Junior Faculty
Project Start Date: January 1, 2013
Project End Date: December 31, 2015
Hepatic mitochondrial dysfunction is a hall marker of NAFLD and insulin resistance. However, whether mitochondrial dysfunction is a causal factor or a consequence of NAFLD and insulin resistance is still controversial.
DsbA-L is a mammalian homology of DsbA, and a versatile player of adiponectin multimerization. By using fat-specific DsbA-L transgenic mice, they found that overexpression of DsbA-L protects mice against diet-induced insulin resistance and NAFLD. But DsbA-L exerts the role in favoring energy homeostasis in vivo independent on adiponectin action. Their preliminary data found that DsbA-L is highly expressed in liver, localized in mitochondria, interacts with mitochondrial Complex I, and plays a critical role in regulating mitochondria function, indicating the protective effect of DsbA-L on liver energy homeostasis.
In the current study, they will test if manipulating mitochondrial function by overexpression or specific-deletion of DsbA-L gene in liver could affect hepatocyte function and systematic energy homeostasis and insulin sensitivity by using in vitro, ex vivo, and unique animal models they generated.
Their studies are highly significant for the following reasons: 1). The unique animal models (liver-specific DsbA-L KO mice) will let them demonstrate for the first time the physiological roles of DsbA-L in the regulation of energy homeostasis in vivo; 2) Their study may lead to the identification of potential new drug targets for effective therapeutic treatment of insulin resistance and its associated medical complications; and 3) Completion of this research will lead to elucidate the importance of hepatic mitochondrial dysfunction in the development of NAFLD and insulin resistance.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and curing diabetes?
Our project covers liver steatosis and insulin resistance. Our study will lead to elucidating of the importance of hepatic mitochondrial dysfunction in the development of nonalcoholic fatty liver disease (NAFLD), insulin resistance and other related disorders such as type 2 diabetes, and provide important information for identification of a potential therapeutic target for the prevention and treatment of insulin resistance and 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?
Our study may lead to the identification of potential new drug targets for effective therapeutic treatment of insulin resistance and its associated medical complications.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
Firstly, my major is Biochemistry, and I am very interested in the study of cell metabolism which is tightly related to diabetes, one typical metabolic disease. Secondly, my grandpas from both mother and father side died from diabetes or its complication cardiovascular disease, and my father in law is a patient with diabetes for 10 years. Thus my study mainly focus on the molecular basis of the development of insulin resistance and type 2 diabetes in order to identify novel therapeutic targets for the treatment of this particular diseases and its related disorders.
This award will help me to move forward to independence of my research career. Upon receiving this award, I am able to make rapid progress to expand the data to apply for more independent funding, including an R01 grant. In addition, this award makes me more competitive when applying for a tenure-track faculty position.
In what direction do you see the future of diabetes research going?
Identification of more novel targets for the prevention and treatment of obesity, insulin resistance and type 2 diabetes.
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