Induction of intestinal peptide transporter 1 expression during fasting is mediated via peroxisome proliferator-activated receptor α
| Autor: | Ken-ichi Inui, Hirofumi Saito, Toshiya Katsura, Jin Shimakura, Tomohiro Terada |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Physiology Peroxisome proliferator-activated receptor Peptide Fatty Acids Nonesterified Ligands Peptide Transporter 1 Mice Pharmacokinetics Physiology (medical) Internal medicine medicine Animals Humans PPAR alpha RNA Messenger Rats Wistar Cells Cultured Mice Knockout chemistry.chemical_classification Messenger RNA Symporters Hepatology biology Body Weight Peptide transporter 1 Gastroenterology Fasting Small intestine Rats Pyrimidines Endocrinology medicine.anatomical_structure chemistry Caco-2 biology.protein Acyl-CoA Oxidase Caco-2 Cells Cotransporter |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 291:G851-G856 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00171.2006 |
| Popis: | We previously demonstrated that starvation markedly increased the amount of mRNA and protein levels of the intestinal H+/peptide cotransporter (PEPT1) in rats, leading to altered pharmacokinetics of the PEPT1 substrates. In the present study, the mechanism underlying this augmentation was investigated. We focused on peroxisome proliferator-activated receptor alpha (PPARalpha), which plays a pivotal role in the adaptive response to fasting in the liver and other tissues. In 48-h fasted rats, the expression level of PPARalpha mRNA in the small intestine markedly increased, accompanied by the elevation of serum free fatty acids, which are endogenous PPARalpha ligands. Oral administration of the synthetic PPARalpha ligand WY-14643 to fed rats increased the mRNA level of intestinal PEPT1. Furthermore, treatment of the human intestinal model, Caco-2 cells, with WY-14643 resulted in enhanced PEPT1 mRNA expression and uptake activity of glycylsarcosine. In the small intestine of PPARalpha-null mice, augmentation of PEPT1 mRNA during fasting was completely abolished. In the kidney, fasting did not induce PEPT1 expression in either PPARalpha-null or wild-type mice. Together, these results indicate that PPARalpha plays critical roles in fasting-induced intestinal PEPT1 expression. In addition to the well-established roles of PPARalpha, we propose a novel function of PPARalpha in the small intestine, that is, the regulation of nitrogen absorption through PEPT1 during fasting. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|