【摘 要】
：
Insulin resistance is a central metabolic defect of type 2 diabetes.As our studies strongly indicate ectopic accumulation of lipids as a primary cause of insulin resistance,we investigated different a
【机 构】
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Diabetes and Obesity Research Program The Garvan Institute of Medical Research Australia
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Insulin resistance is a central metabolic defect of type 2 diabetes.As our studies strongly indicate ectopic accumulation of lipids as a primary cause of insulin resistance,we investigated different approaches for the reversal of insulin resistance by reducing ectopic lipid accumulation.To test this concept,our examined pharmacological agents influencing lipid metabolism by activating either transcription factors PPARg and PPAR a or AMPK-a key enzyme mediating fat oxidation.We then extended the concept to explore the discovery of new antidiabetic components from traditional Chinese medicines (TCM).Our discovery research started with the application of the concepts from above studies to the evaluation TCM to select candidates.We next screened those compounds isolated or derivatized from the selected TCM in cell-based GLUT4 translocation/glucose uptake assays.Promising compounds were further assessed for their effects on the PI3K/Akt and AMPK pathways known to mediate GLUT4 translocation and investigated for the molecular mechanisms involved.Finally,optimized leads were chosen for detailed evaluation of their efficacy on glucose intolerance and insulin resistance in animal models.From these approaches we have discovered and developed antidiabetic berberines and triterpenoids involving AMPK by different mechanisms.
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