The role of PAS Kinase in insulin-induced lipogenesis
Focus: Diabetic Dyslipidemia, Insulin Action\Metabolism, Insulin Action\Transgenic Models
Type of Grant: Mentor Based Postdoctoral Fellowship
Project Start Date: July 1, 2011
Project End Date: June 30, 2015
Obesity is a very potent risk factor for type 2 diabetes. One of the reasons for this is likely to be the increased level of fat found throughout the body. The liver plays an important role in making that fat and this process appears to be inappropriately accelerated in conditions of diabetes and related metabolic syndromes. The proteins that control and carry out this pathway have begun to be discovered. We have found a new protein that seems to play a key role in controlling this pathway both in intact animals and in isolated cells grown in the petri dish. The major goal of this project is to determine how this protein acts to control the fat production pathway and how important this specific protein is in animal models of diabetes. If the hypothesis of this project proves correct, we will have found a new target that can be explored in the treatment of diabetes and the associated problems with impaired fat handling.
Mentor: Rutter, Jared, PhD Postdoctoral Fellow: Fogarty, Sarah
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This project relates to the severe problem that typically accompanies pre-diabetes and type 2 diabetes of accelerated fat synthesis in the liver. This problem is believed to play an important role in the 'vicious cycle' that promotes the eventual failure of the pancreatic beta-cells and overt diabetes.
This project is focused on the role of one specific protein, PAS kinase, in mediating the pathological fat synthesis. We have strong evidence that this protein is involved and we are now in need of information about how this protein works and how it is regulated. The portion of this project funded by the ADA will determine which other proteins PAS kinase works with to promote fat synthesis. It will also explore the role in animal models of PAS kinase in promoting fat synthesis.
Why is it important for you, personally, to become involved in diabetes research?
There are still many aspects of diabetes that we don't understand. One of them is the role of fat in the liver (and elsewhere) in promoting insulin resistance and type 2 diabetes. The protein on which we focus is involved in the generation of this fat. If it acts the way that we think it does, it could be a new target for development of therapeutics for diabetes. We are actively exploring this possibility and have early positive results.
What role will this award play in your research efforts?
This award is to fund the research of a very talented postdoctoral fellow, Sarah Fogarty, in my laboratory. This will free up resources that can now be used to conduct experiments and make discoveries. The prevalence and devastation of diabetes make it imperative for us to find new and better ways to treat this disease.
In what direction do you see the future of diabetes research going?
I see the research in my laboratory going in multiple directions in the future. First, we want to understand how insulin promotes fat biosynthesis. What are the proteins involved and how do they work together? Second, we want to determine the physiological states in which this is the most important in animals. Finally, we are pursuing therapeutics that will target this pathway for the treatment of diabetes and dyslipidemia. In the end, the product of my research should be a direct benefit to the treatment, prevention or understanding of diabetes and related diseases.
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