Research Outline

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  Type II diabetes is primarily associated with insulin resistance and β-cell dysfunction.  The β-cell is a highly specialized cell with a unique metabolic profile and able to sense fluctuations in circulating blood glucose and lipid levels.  Hyperglycemia and hyperlipidemia from increasing obesity and insulin resistance leads to a loss of the unique expression patterns of genes necessary for appropriate insulin secretion and causes β-cell malfunction (gluco/lipotoxicity) and, ultimately, death (gluco/lipoapoptosis) of the affected cells.  Intracellular homeostasis of lipids and other substrates is essential for cellular health and function.
  
  Nuclear receptors are ligand-activated transcription factors that coordinate gene expression in response to hormonal and environmental signals. Members of the superfamily that work as heterodimers with the retinoid X receptor (RXR) serve as sensors of dietary components, orchestrating the physiological response to nutrients. Although nuclear hormone receptors have been extensively studied in liver, adipose tissue, and macrophages, the importance for development and metabolism of endocrine pancreas is not as well characterized.  The expressions and activities of some nuclear hormone receptors such as peroxisome proliferator-activated receptors (PPAR), SHP, VDR, and ERR are related with pancreatic islet morphology and/or β-cell function although their mechanism is not fully understood.
  

Research Contents

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  1. Role of Nuclear Receptors in Metabolic Disease
  2. Nuclear Receptors Regulating Endocrine Pancreas Function
      - The consequences of β-cell Liver X Receptor (LXR) action on glucose homeostasis
      1) determine the role of β-cell specific activation of LXR in the maintenance of glucose homeostasis
      2) determine the islet phenotypes and measure the metabolic parameters such as
          ATP/ADP, glucose oxidation, fatty acid synthesis and oxidation, and triglyceride
      3) Determine the effects of diet and age on βLXRTG phenotype.
  3. Transcription Factors and Gene Expression
  4. The Roles of Carbohydrate Responsive Element Binding Protein (ChREBP) in Glucose  Metabolism
  5. Gene Therapy
  

About LAB

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  We are studying the roles of orphan nuclear hormone receptors in β-cells, and whether their levels are altered by nutrients, drugs, or other transcriptional regulators. Our extensive understanding of how pancreatic β-cells work and the role of free fatty acids and triglycerides in the regulation of normal insulin secretion and in the β-cell dysfunction of diabetes is crucial to identify and design therapeutic interventions aimed at ameliorate diabetes.

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