I and type II diabetic mice M H had Silodosin adrenergic receptor inhibitor significantly Here hepatic and ileal FGF15 expression of SHP mice than the wild-type M-. These data show that in diabetic conditions, the positive effect of glucose may dominate the negative effect of FGF15 and SHP in the contr Of the CYP7A1 gene transcription. Both STZ treated and ob / ob mice had M 3 5-fold higher Serum bile here And bile acids pool Acid 30%. Interestingly, the analysis of the S Acid composition of gall bladder is a tendency to increased Taurochols Acid and S Acid tauromuricholic decrease, resulting in an hour Higher index of bile Acid hydrophobicity in wild-type from0.41 to 0.2 in the STZ-M mice and ob / ob analysis of F chemicals Gallen acid composition showed that more diabetic M mice Chols acid and Desoxychols acid and muricholic S acids less than the wild-type M mice excreted. Chols acid A lower critical micelle concentration, therefore it is effective to facilitate the intestinal absorption of cholesterol. This may be the absorption of cholesterol in the intestine markedly Ago fractional diabetic M Mice compared to wild-type M Mice and can be connected to hypercholesterolemia Chemistry in diabetic M Mice contribute to explained Ren. Refeeding stimulated CYP7A1 expression in CYP7A1 humanized M Tg mice but not in diabetic mice M, It is now well documented that the transcription of the human and mouse CYP7A1genes is differentially regulated by di t, I You, insulin / glucagon, and the circadian rhythm. There is considerable variation in the CYP7A1 promoter sequences of genes in different species.
It is unclear whether differences in the type CYP7A1 gene regulation by genomic effects or epigenetic mechanisms. Study of the human CYP7A1 gene regulations is limited to models of human hepatocytes. To clarify the regulation of human N Drastic decrease CYP7A1 gene expression study in an in vivo system, we have Tg mice M, A humanized CYP7A1 CYP7A1 copy of the human CYP7A1 gene knock-out Mice House on a background. The CYP7A1 humanized tg M Mice Gruppengr one Of bile acids e Compared with the mice of wild-type M-. Composition of bile in the gall bladder CYP7A1 humanized Tg-M Mice was slightly modified, a slight Etoposide SRC inhibitor increase in Chols Acid and a decrease in muricholic S Acids and mice compared to wild-type M-. CYP7A1 nozzles humanized Tg M With S Acid binding resin cholestyramine strong induction of CYP7A1 human mRNA. In contrast to the mouse CYP7A1, which was induced by feeding cholesterol through the activation of LXR, has foods CYP7A1 humanized Tg Mice with a high cholesterol-di t with 2% non-induced, but suppresses CYP7A1 mRNA expression. This is consistent with the absence of a LXR-binding site on the human CYP7A1 gene promoter. Together, these results indicate that the human CYP7A1 in the transgenic M Nozzles functional in the preparation of an active enzyme. Refeeding significantly CYP7A1 mRNA in CYP7A1 humanized Tg mice M Induced, increases hte histone H3 acetylation and decreased histone H3K9 trimethylation of FOXO1 and reduced occupancy of the human CYP7A1 gene promoter. In addition, diabetic M Tg mice humanized CYP7A1 mRNA was significantly h Ago basal CYP7A1, histone acetylation 4, the Poolgr E of bile Acids and bile acid In serum compared to control aids STZ treated mice. In summary, provided this information is the first in vivo evidence that the human CYP7A1 gene was induced.