Dept. of Medicine
Division of Endocrinology, Diabetes and Metabolism
Yonsei University, Seoul, Korea
BS, Food and Nutrition, 1984
Yonsei University, Seoul, Korea
MS, Biochemistry, 1986
Iowa State University
PhD, Genetics, 1997
Pennsylvania State University
Postdoctoral Fellow, Cellular and Molecular Pathology, 1997-9
Insulin resistance is centered in the pathogenesis of cardiometabolic syndrome. My current research focuses on understanding the mechanisms of insulin resistance and endothelial dysfunction caused by pro-inflammatory signaling. This includes identification and characterization of specific kinases that impair insulin signaling in both metabolic and cardiovascular tissues. In related studies, I am investigating mechanisms for bioactive polyphenols to ameliorate cardiovascular and metabolic diseases.
Cross-talk between inflammation and insulin signaling– Obesity, insulin resistance, dyslipidemia, and hypertension cluster together in the metabolic syndrome. Inflammatory signaling pathways activate various kinases that impair insulin signaling resulting in insulin resistance. My first project is focused on investigating the signaling pathways that are activated by high fat diet, which leads to stimulation of inflammatory signaling. One hypothesis regarding fatty acid-induced inflammatory signaling is that production of reactive oxygen species leads to activation of IKKb. Recently, it has been reported that free fatty acids specifically activate Toll-like receptors. The activation of Toll-like receptors is involved in high fat diet induced insulin resistance and cardiovascular diseases. However, the detailed mechanism between toll-like receptor and dietary fat is not clearly understood. I plan to elucidate molecular mechanisms for fatty acids to activate toll-like receptors and related signal transduction pathways. In addition, I plan to investigate the regulation of genes by fatty acid stimulation through toll-like receptors. The results of this project will help us to understand the molecular mechanisms underlying high fat diet induced insulin resistance and endothelial dysfunction.
Polyphenolic compounds that ameliorate insulin resistance and endothelial dysfunction – Polyphenols in green tea (EGCG), red wine (resveratrol), citrus fruit (naringenin), and chocolate (epicatechin) have vasodilator actions that may ameliorate hypertension and insulin resistance. I have been studying the biological actions of EGCG, especially with regard to endothelial function. We found that EGCG activates eNOS and NO production through a Fyn dependent mechanism. We also observed that hesperetin and naringenin to promote vasodilation and anti-inflammatory effects through activation of PI 3-kinase/Akt, and/or AMPK/eNOS/NO pathways. In related studies, I would like to examine whether various polyphenolic compounds can inhibit inflammatory signaling pathways and improve fatty acid-induced insulin resistance. These studies may give additional novel insights related to molecular mechanisms for insulin resistance and endothelial dysfunction.
Linking inflammation with the metabolic syndrome is highly relevant to major public health problems. The results of these projects may contribute to prevention and treatment of cardiovascular and metabolic diseases.
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