Hedrick, Catherine , PhD
Natural Killer (NK) cell function in Type 2 diabetic subjects.
General Research Subject: Type 2 Diabetes
Focus: Complications, Complications\Macrovascular-Cellular Mechanisms of Atherogenesis in Diabetes, Immunology
Project Start Date: January 1, 2013
Project End Date: December 31, 2013
Diabetes Type: Type 2 diabetes
Natural killer cells (NK) are lymphocytes that function as early rapid responders to inflammatory insults, including viruses, bacteria, cancer cells and damaging oxidized lipids that are generated by elevated low-density lipoprotein (LDL) levels. NK cells serve two functions: 1) to rid the body of damaging cells or pathogens via killing or cytotoxic action, or 2) to activate T lymphocyte functions by triggering activation of macrophages and dendritic cells. Although considered a 'protective' cell type, we hypothesize that NK cells become damaging if activated during chronic diseases, such as in type 2 diabetes (T2D) and obesity. NK cells may also contribute to complications of T2D, such as atherosclerosis.
In this proposal, we will obtain peripheral blood from human control subjects and subjects with T2D, who have had clinically measured scores of extent of atherosclerosis using either coronary angiography or intimal medial thickness measures using ultrasound. Using each subject's blood, we will: a) determine numbers and activation status of NK cells in subjects with T2D to compare with normal control subjects, and b) within the T2D population, establish associative correlations with NK numbers and phenotypes and degree of atherosclerosis (cardiovascular disease) using IMT and angiographic data that will be provided to us on each patient. The results of this study will provide novel insights into the activation status of NK cells in human subjects with T2D and will allow us to determine if regulation of NK cell function is important for the cardiovascular complications of this disease.
Mentor: Catherine C. Hedrick
Undergraduate: La Teira Haynes
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and curing diabetes?
The research proposed in our project centers around complications of T2D related to cardiovascular disease. Subjects with T2D are 5 times more likely to suffer a heart attack than someone without T2D. Atherosclerosis is plaque formation in the artery that is caused by high cholesterol and changes in inflammation and immune cell function. Atherosclerosis is the underlying cause of cardiovascular disease. Immune cells normally help fight infection and disease. Natural killer cells (NK) are immune cells that function as early rapid responders to inflammatory insults, including viruses, bacteria, cancer cells and damaging oxidized lipids that are generated by elevated low-density lipoprotein (LDL) levels.
NK cells serve two functions: 1) to rid the body of damaging cells or pathogens via killing or cytotoxic action, or 2) to activate T lymphocyte functions by triggering activation of macrophages and dendritic cells. Although considered a 'protective' cell type, we hypothesize that NK cells become damaging if chronically activated in diseases, such as T2D and obesity. NK cells may also contribute to complications of T2D, such as atherosclerosis. The results of this study will provide novel insights into the activation status of NK cells in human subjects with type 2 diabetes and will allow us to determine if regulation of NK cell function is important for the cardiovascular complications of this disease.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Our project will inform us about how early responder lymphocytes, including natural killer cells, are changed in subjects with T2D. These cells normally function to rid the body of viruses and other pathogens. This information is important as it will provide novel information as to whether these cells get activated or changed during T2D progression and how such activation may contribution to macrovascular complications of T2D, including heart disease. If the function of these cells is altered in a negative manner in subjects with T2D, it could also lead to defective clearance of viruses in T2D subjects, thereby explaining in part why diabetics often are more susceptible to influenza and other viruses.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?
I realize that the incidence of T2D and obesity is increasing at enormous rates in the US. I also know that childhood obesity and T2D is becoming a major US health issue. I have an 8-year old son, and I want him to remain healthy. I am quite interested in making people aware of the cardiovascular health risks associated with childhood obesity and diabetes. Moreover, as incidence of having a heart attack is 4x higher in a patient with T2D versus someone without diabetes, as a researcher, I am interested in trying to understand mechanisms for this accelerated disease aspect and how to develop therapeutics that may help others, including these children that will someday grow up and have to face cardiovascular disease complications.
In what direction do you see the future of diabetes research going?
The future of diabetes research will be to a) further understand how adipocytes and obesity impact inflammation, which impacts T2D onset and duration, and b) try to develop novel therapies that reduce inflammation and immune responses associated with T2D as they relate to cardiovascular disease.
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