ArticleActa pharmacologica Sinica2020
Diabetes downregulates peptide transporter 1 in the rat jejunum: possible involvement of cholate-induced FXR activation.
Article in Acta pharmacologica Sinica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 19 citations in OpenAlex.
- Mechanisms and therapeutic advances of gut metabolites in the regulation of neuroimmune inflammatory diseases.Frontiers in immunology · 2026Review
- Identification and validation of biomarkers related to mitochondria-associated endoplasmic reticulum membranes in type 2 diabetes mellitus using peripheral blood transcriptomics.European journal of medical research · 2025Article
- Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.Nature metabolism · 2024Article
- Konjac supplementation can alleviate obesity induced by high-fat diet in mice by modulating gut microbiota and its metabolites.Current research in food science · 2024Article
- Urine metabolomics reveals biomarkers and the underlying pathogenesis of diabetic kidney disease.International urology and nephrology · 2023Article
- Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.Acta pharmaceutica Sinica. B · 2023Article
- Article
- Amentoflavone-EnrichedLife (Basel, Switzerland) · 2022Article
- Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway.Frontiers in pharmacology · 2021Article
- Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance.Pharmaceutics · 2020Review
- Effect of different bile acids on the intestine through enterohepatic circulation based on FXR.Gut microbesReview
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7 authors at 1 institution in 1 country.
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Abstract
Peptide transporter 1 (PepT1), highly expressed on the apical membrane of enterocytes, is involved in energy balance and mediates intestinal absorption of peptidomimetic drugs. In this study, we investigated whether and how diabetes affected the function and expression of intestinal PepT1. Diabetes was induced in rats by combination of high-fat diet and low dose streptozocin injection. Pharmacokinetics study demonstrated that diabetes significantly decreased plasma exposures of cephalexin and acyclovir following oral administration of cephalexin and valacyclovir, respectively. Single-pass intestinal perfusion analysis showed that diabetes remarkably decreased cephalexin absorption, which was associated with decreased expression of intestinal PepT1 protein. We assessed the levels of bile acids in intestine of diabetic rats, and found that diabetic rats exhibited significantly higher levels of chenodeoxycholic acid (CDCA), cholic acid (CA) and glycocholic acid (GCA), and lower levels of lithocholic acid (LCA) and hyodeoxycholic acid (HDCA) than control rats; intestinal deoxycholic acid (DCA) levels were unaltered. In Caco-2 cells, the 6 bile acids remarkably decreased expression of PepT1 protein with CDCA causing the strongest inhibition, whereas TNF-α, LPS and insulin little affected expression of PepT1 protein; short-chain fatty acids induced rather than decreased expression of PepT1 protein. Farnesoid X receptor (FXR) inhibitor glycine-β-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). In diabetic rats, the expression of intestinal FXR protein was markedly increased. Oral administration of CDCA (90, 180 mg·kg
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