Bajaj, Mandeep , MD
NF-kappaB Inducing Kinase and insulin resistance
General Research Subject: Type 2 Diabetes
Focus: Insulin Action, Insulin Action\Insulin Resistance, Insulin Action\Metabolism, Integrated Physiology, Integrated Physiology\Muscle
Type of Grant: Translational Science
Project Start Date: July 1, 2013
Project End Date: June 30, 2016
Diabetes Type: Type 2 diabetes
In the proposed project, we plan to study the role of a novel inflammatory mechanism involving NFkappaB-Inducing Kinase (NIK), a key protein regulating inflammation and insulin resistance. Our overall goal is to study the role of NIK in causing insulin resistance in the muscle via inflammation. First, we will study obese as well as type 2 diabetic human subjects and explore how elevated levels of NIK can be altered by weight loss leading to improved insulin sensitivity. Second, using cultures of human skeletal muscle obtained from the clinical study biopsies, we will explore potential mechanisms responsible for the elevation of NIK and elucidate the mechanism(s) by which fat derived proteins can change NIK protein levels in skeletal muscle of obese and type 2 subjects therby providing the link between obesity and diabetes.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
Obesity is associated with insulin resistance in the muscle and liver and an increased risk to develop type 2 diabetes. Insulin resistance is associated with skeletal muscle inflammation. Adiponectin is an insulin-sensitizing adipocytokine that is secreted by fat cells and it enhances the ability of insulin to dispose glucose in the skeletal muscle. Circulating adiponectin levels are decreased in obesity and type 2 diabetes and are associated with skeletal muscle insulin resistance. My laboratory proposes to study the molecular mechanisms by which adiponectin inhibits skeletal muscle inflammation and enhances skeletal muscle insulin sensitivity with a focus on novel skeletal muscle inflammatory proteins. We shall study the precise mechanisms by which increased circulating adiponectin following weight loss can inhibit skeletal muscle inflammation and improve insulin sensitivity. In addition, we shall study the relationship between these inflammatory proteins and impairment in insulin signaling and the ability of adiponectin to block these deleterious effects.
If a person with diabetes were to ask you how your project will help them in the future,
how would you respond?
By understanding how adiponectin regulates inflammatory proteins in human skeletal muscle, inhibits skeletal muscle inflammation, and enhances muscle insulin sensitivity, we hope to provide novel research findings that can be used to develop therapies for treating diseases characterized by insulin resistance including type 2 diabetes.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Since I was a young child I watched my father work in his laboratory trying to find the answers to questions about diabetes and its complications. It was then that I decided to devote my career to diabetes research and find new and better ways to prevent and treat this disease. I became very interested in understanding the relationship between obesity and insulin resistance and the role played by proteins secreted by fat cells. This award represents a significant encouragement to my research efforts and career.
In what direction do you see the future of diabetes research going?
Diabetes research in the future will focus on the genetics and molecular biology of insulin resistance and insulin secretion abnormalities in type 2 diabetes. It will also have a focus on the molecular mechanisms linking obesity, insulin resistance and cardiovascular disease. Discovering new drugs for the prevention of diabetes would be another important direction for diabetes research.
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