Indeed, FXR exerts a substantial influence on hepatic carbohydrate metabolism and loss of FXR disrupts normal glucose homeostasis and contributes to the development of insulin resistance .
Firstly, hepatic FXR expression is decreased in diabetic animal models and normalized upon insulin supplementation .
Using insulin-deficient diabetic mice model, in vivo experiments demonstrated that FXR activation ameliorated insulin secretion and delayed development of signs of diabetes, hyperglycemia, and glycosuria .
In contrast to the repression of CYP7A1 transcription by FXR, CYP7A1 is transactivated by the oxysterol receptor, LXR[alpha].
The mechanism in coordinated control of nuclear receptors FXR and LXR to keep bile acid levels under restraint has been reviewed by Lu et al.
BAS bind bile acids in the intestine, thus reducing the endogenous ligands for FXR and therefore acting to reduce FXR activation.
Factually, FXR activity is decreased upon Asbt inhibitor administration .
FXR agonists are likely to be effective triglyceride-lowering drugs and they may also have potential benefits in reducing elevated glucose.
What is more, the antiparasitic drug ivermectin has been identified as a novel ligand for FXR recently .
Last but not least, as LXR and FXR are almost ubiquitously expressed, they have been involved in testis  and adrenal  physiologies, thus being associated to reproduction [146,147].
Coordinated actions of nuclear receptors FXR and LXR exert a complex role in transcriptional regulation of genes involved in bile acid, lipid, carbohydrate metabolism, and pancreatic [beta]-cell function (Figure 1).
Mangelsdorf, "LXRs and FXR: the Yin and Yang of cholesterol and fat metabolism," Annual Review of Physiology, vol.