Finding Links between Obesity and Diabetes: Using Diacylglycerol Kinase to Regulate Insulin Signaling Public Deposited

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Last Modified
  • February 26, 2019
Creator
  • Hwarng, Gwen Yung-Hsin
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • In the U.S., two-thirds of adults are overweight or obese, with 35.7% of them - nearly 78 million people – obese. What used to be a disease that only afflicted adults is now also increasingly being diagnosed in children, contributing to ever-growing obesity rates. In particular, obesity and diabetes are closely linked, with obese people at higher risk for developing type 2 diabetes. All this only further intensifies the urgent need to address obesity and type 2 diabetes. In particular, we need to understand how the two conditions are linked and what metabolic processes are involved, in order to develop treatment and prevention strategies that will ultimately reduce the burden of type 2 diabetes on healthcare. My project looks at how the triacylglycerol synthesis and insulin signaling pathways are linked. In particular, we are studying how lipid intermediates cause insulin resistance in hepatocytes. We are interested in whether phosphatidic acid (PA) and diacylglycerol (DAG) affect Akt phosphorylation, and the mechanism by which PA and DAG might inhibit insulin signaling. Diacylglycerol kinase (DGK) is the enzyme that catalyzes conversion of DAG to PA, and was used as a tool to manipulate the cellular content of PA and DAG. The content and activity of DGK was adjusted by DGK overexpression in mouse hepatocytes, thus altering the balance of PA and DAG. The physiological consequences were then used to determine how insulin signaling is affected. Our hypothesis is that DGK regulates insulin signaling by changing intracellular PA and DAG levels. The isoform used was the DGKθ isoform. Our results showed that PA is associated with impaired insulin action in mouse hepatocytes, but DAG is not.
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Rights statement
  • In Copyright
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  • Funding: Tom and Elizabeth Long Excellence Fund for Honors
Advisor
  • Coleman, Rosalind
Degree
  • Bachelor of Science in Public Health
Honors level
  • Highest Honors
Degree granting institution
  • University of North Carolina at Chapel Hill
Extent
  • 31
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