Technical Name Develop of novel anti-diabetic agents via targeting endogenous lipid mediators
Project Operator National Taiwan University
Project Host 莊立民
Summary PPARγ is the master regulator of glucose metabolism.15-keto-PGE2 is an endogenous PPARγ ligand whitch is degraded by ZADH1. We found that increasing 15-keto-PGE2 promotes glucose uptake. We identified several ZADH1 inhibitors which could increase 15-keto-PGE2 promote glucose uptake via activating PPARγ. Our results showed that inhibition of ZADH1 is a novel approach to treat type 2 diabes mell
Scientific Breakthrough The widely used ant-diabetic agent, thiazolidinedione (TZD) lower glucose by activating PPARγ. However, TZD has significant side effects including weight gain, water retention,osteoporosis. We found that 15-keto-PGE2 is an endogenous PPARγ ligand. Inhibiting ZADH1, the degradating enzyme of 15-keto-PGE2, could increase 15-keto-PGE2promote glucose uptakeis a novel strategy for treating diabetes
Industrial Applicability Diabetes mellitus is a global epidemic disease. TZD is widely used to treat diabetes mellitus. However, it is associated with several adverse side effects. The development of ZADH1 small molecule inhibitor is a novel therapeutic strategy for treating diabetes without the side effect of TZD.
Keyword Diabetes mellitus 15-keto-PGE2 ZADH1 high-throughput screening structured-based drug design small molecule inhibitor Peroxisome proliferator-activated receptor gamma adipogenesis glucose uptake Thiazolidinedione (TZD)
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