Figure 5.

GLP-2 treatment interferes with bile acid homeostasis in Mdr2^-/-mice. Real-time polymerase chain reaction was used to assess the mRNA expression of (A) Fxr, Car, Pxr, and Pgc1α, (B) Cyp7a1, Cyp8b1, Cyp27, and Cyp2c70, (C) Cyp2b10 and Cyp3a11, and (D) Bsep and Ntcp in the liver. mRNA levels of Fxr were significantly lowered, whereas Car, Pxr, and Pgc1α were increased. Cyp7a1 was significantly lowered because of GLP-2 treatment in Mdr2^-/- mice, whereas Cyp8b1 and Cyp27 remained unchanged and Cyp2c70 was increased. Gene expression of detoxification enzymes Cyp2b10 and Cyp3a11 was significantly increased because of GLP-2. Although Bsep expression levels tended to be lowered, Ntcp showed a tendential increase. mRNA expression values were normalized against 36b4 levels and are shown relative to the expression level in Mdr2^-/- control subjects. ∗Significant difference from Mdr2^-/- control mice; P < .05. (E) Hepatobiliary bile flow and bicarbonate (HCO₃^-) output were assessed. Neither bile flow nor HCO₃^- output was changed because of GLP-2 treatment. (F) Representative electrophoretic mobility shift assay demonstrated that GLP-2 treatment suppresses the nuclear binding of FXR, whereas GW4064 (FXR agonist) challenge led to an increase of FXR nuclear binding. Ab, antibody; C, cytoplasmatic protein fraction; N, nuclear protein fraction.