Ntc S Dictionary Of Everyday American English Expressions Pdf
Ntc S Dictionary Of Everyday American English Expressions Pdf
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Download! Download! Download! Download! Download! Download! Download! Download! Download!Farnesoid X receptor (FXR) is a nuclear hormone receptor activated by bile acids and essential for normal homeostasis. FXR deficiency results in severe metabolic diseases such as obesity and diabetes, but the molecular mechanisms by which FXR regulates energy homeostasis is poorly understood. In addition, while the pharmacological effects of the FXR agonist T-CA are well defined, the pharmacological actions of FXR?s endogenous ligand, chenodeoxycholic acid (CDCA), is not well characterized. We have recently found that FXR binds to and activates the mouse Trp58 G protein- coupled receptor (TGR5) that is expressed in the enterohepatic system where it regulates bile acid and glucose homeostasis. We will test the overall hypothesis that CDCA, together with bile acids, serve as FXR-targeting signals to regulate lipid and carbohydrate homeostasis in the liver. We will first address the following specific aims: 1) Mechanism of FXR-mediated TGR5 activation. We will test the hypothesis that FXR modulates the ligand-induced activation of TGR5 through both genomic and non-genomic mechanisms in a cell-specific manner. Second, we will assess the roles of TGR5 and FXR in bile acid signaling and glucose homeostasis in vivo in mice and explore the pharmacological effects of CDCA. 2) Genetic assessment of FXR and TGR5 in diverse genetic models of impaired glucose and lipid homeostasis and mouse phenotypic modeling of FXR deficiency. We will investigate the roles of FXR and TGR5 in mediating the effects of bile acid and FXR agonist T-CA on glucose, lipid and bile acid homeostasis. In addition, by genetic assessments in knockout mice and gene function studies in human cells, we will explore the potential roles of FXR and TGR5 in genetic models of impaired glucose and lipid metabolism. 3) Molecular characterization of the FXR/TGR5 signaling pathway. We will assess the role of FXR in TGR5- mediated bile acid signaling
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