Activation of the Akt (insulin signaling pathway) and FXR by bile acids in hepatocytes

Activation of the Akt (insulin signaling pathway) and FXR by bile acids in hepatocytes. Taurocholate (TCA) activates the AKT pathway via a Gαi protein;coupled receptor(s). Phosphoinositide-dependent protein kinase 1 (PDK-1), a kinase in the insulin signaling pathway, then activates atypical protein kinase C ζ (PKCζ). Activated PKCζ is proposed to phosphorylate FXR, enhancing its ability to bind TCA and induce the gene encoding SHP. Activated Akt phosphorylates the transcription factor FOX01. The phosphorylated form of FOX01 exits the nucleus, allowing for the downregulation of gluconeogenic genes [PEP carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase)]. Akt also phosphorylates glycogen synthase kinase 3 (GSK-3), inactivating this kinase, which allows for the dephosphorylation and activation of glycogen synthase activity. NTCP, Na+/taurocholate cotransporting polypeptide; DCA, deoxycholic acid; Src, src family kinases; EGFR, epidermal growth factor receptor; PTP, phosphotyrosine phosphatase; PTX, pertussis toxin; IR, insulin receptor.

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Bile acids as regulatory molecules. (2009) Phillip B. Hylemon, et al. J Lipid Res. 2009 Aug;50(8):1509-1520. Figure: F6. All organisms Homo sapiens Drosophila melanogaster

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