Human glucocorticoid receptor (GR) is a protein encoded by the gene NR3C1 (Nuclear Receptor Subfamily 3, Group C, Member 1). GR functions as both a transcription factor binding glucocorticoid response elements to activate transcription of genes as well as a regulator of other transcription factors. Glucose HomeostasisGlucocorticoids (GC) are involved extensively in the regulation of physiological glucose levels. GluconeogenesisGluconeogenesis occurs mainly in the liver to generate glucose from non-carbohydrate substrates such as lactate, glycerol, and gluconeogenic amino acids such as alanine[1]. insert pathway GC increase the activity of gluconeogenesis in hepatic cells predominantly by activating the transcription of genes encoding gluconeogenic enzymes such as pyruvate carboxylase (PC), cytosolic phosphoenolpyruvate carboxykinase (PCK1), fructose-1,6-bisphosphatase 1 (FBP1), phosphofructokinase 2/fructose bisphosphatase 2 complex (PFKFB1), glucose-6-phosphatase catalytic subunit (G6PC), and glucose-6-phosophate (G6P) transporter[1]. GC coordinate with an intracellular glucocorticoid receptor (GR) to initiate signal transduction. Prior to the GC/GR binding however, GR is complexed with a chaperone Hsp90 in the cytoplasm. Upon binding of the GC to the GR, the Hsp90 chaperone dissociates from the GR and the resulting GR/GC complex enters the nucleus[1]. The GR is then recruited to specific genomic sequences called glucocorticoid response elements (GRE) [1].
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This page was last modified 13:57, 31 January 2017.