Glucose regulates the expression of the farnesoid X receptor in liver.
| Autor: | Duran-Sandoval, Daniel, Mautino, Gisèle, Martin, Geneviève, Percevault, Fréderic, Barbier, Olivier, Fruchart, Jean-Charles, Kuipers, Folkert, Staels, Bart, Mautino, Gisèle, Martin, Geneviève, Percevault, Fréderic |
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| Předmět: |
HYPERTRIGLYCERIDEMIA
GALLBLADDER diseases DIABETES complications MESSENGER RNA BIOCHEMISTRY PEOPLE with diabetes LIVER physiology ANIMAL experimentation CELL receptors COMPARATIVE studies DIABETES DNA probes DYNAMICS EPITHELIAL cells GENES GLUCOSE INSULIN LIVER RESEARCH methodology MEDICAL cooperation NUCLEOTIDES POLYMERASE chain reaction RATS RESEARCH RNA TRANSCRIPTION factors DNA-binding proteins EVALUATION research CELL physiology |
| Zdroj: | Diabetes; Apr2004, Vol. 53 Issue 4, p890-898, 9p, 1 Black and White Photograph, 7 Graphs |
| Abstrakt: | An increased prevalence of hypertriglyceridemia and gallbladder disease occurs in patients with diabetes or insulin resistance. Hypertriglyceridemia is positively associated to gall bladder disease risk. The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor that plays a key role in bile acid and triglyceride homeostasis. The mechanisms controlling FXR gene expression are poorly understood. This study evaluated whether FXR gene expression is regulated by alterations in glucose homeostasis. FXR expression was decreased in livers of streptozotocin-induced diabetic rats and normalized upon insulin supplementation. Concomitantly with diabetes progression, FXR expression also decreased in aging diabetic Zucker rats. In primary rat hepatocytes, D-glucose increased FXR mRNA in a dose- and time-dependent manner, whereas insulin counteracted this effect. Addition of xylitol, a precursor of xylulose-5-phosphate, to primary rat hepatocytes increased FXR expression to a comparable level as D-glucose. Finally, expression of the FXR target genes, SHP and apolipoprotein C-III, were additively regulated by D-glucose and FXR ligands. This study demonstrates that FXR is decreased in animal models of diabetes. In addition, FXR is regulated by glucose likely via the pentose phosphate pathway. Dysregulation of FXR expression may contribute to alterations in lipid and bile acid metabolism in patients with diabetes or insulin resistance. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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