Intestinal uptake of nateglinide by an intestinal fluorescein transporter

Abstract

Nateglinide, a novel oral hypoglycemic agent, rapidly reaches its maximum serum concentration after oral administration, suggesting that it is rapidly absorbed in the intestine. However, nateglinide itself is not transported by MCT1 or PEPT1. The aim of this study was to characterize the transporters on the apical side of the small intestine that are responsible for the rapid absorption of nateglinide. It has been reported that the uptake of fluorescein by Caco-2 cells occurs via an H+-driven transporter and that the intestinal fluorescein transporter is probably not MCT1. We examined the contribution of the fluorescein transporter to the uptake of nateglinide by Caco-2 cells. Fluorescein competitively inhibited H+-dependent nateglinide uptake. All of fluorescein transporter inhibitors examined reduced the uptake of nateglinide. Furthermore, nateglinide inhibited fluorescein uptake. We conclude that the intestinal nateglinide/H+ cotransport system is identical to the intestinal fluorescein/H+ cotransport system.

Characterization of Monocarboxylate Transporter 6: Expression in Human Intestine and Transport of the Antidiabetic Drug Nateglinide

“…In this study, we investigated the expression of MCT6 in the human small intestine and compared the transport properties of nateglinide via MCT6 with those previously reported for Caco-2 cells (Okamura et al, 2002;Itagaki et al, 2005a). Our results indicated that MCT6 is located on the apical side of human intestinal villous epithelial cells and mediates the transmembrane transport of nateglinide, suggesting that MCT6 may be involved in the absorption of nateglinide.…”

“…Nateglinide Transport via MCT6 1885 at ASPET Journals on May 12, 2018 dmd.aspetjournals.org been shown to inhibit uptake of nateglinide by Caco-2 cells (Okamura et al, 2002;Itagaki et al, 2005a), did not affect the MCT6-specific uptake of [ 14 C]nateglinide (Fig. 5).…”

“…Previous studies have shown that the uptake of nateglinide by the human colon adenocarcinoma cell line Caco-2 occurs via an H + -driven transport system (Okamura et al, 2002) and a fluorescein/H + cotransport system (Itagaki et al, 2005a). In rat intestinal brush-border vesicles, it has been shown that the ceftibuten/H + cotransport system, which is identical to the fluorescein/H + cotransport system, is involved in the uptake of nateglinide (Itagaki et al, 2005b;Saito et al, 2006).…”

Non-Involvement of the Human Monocarboxylic Acid Transporter 1 (MCT1) in the Transport of Phenolic Acid

“…hMCT1, human MCT1. cells, 20) which was identical to the ferulic/H þ cotransport system. 21) Therefore, the transepithelial transport and uptake of fluorescein were measured in Caco-2 cells treated with NaBut or transfected with human MCT1 (Figs.…”

Purification by p-aminobenzoic acid (PABA)-affinity chromatography and the functional reconstitution of the nateglinide/H+ cotransport system in the rat intestinal brush-border membrane

“…Since we have reported that benzoic acid and salicylic acid significantly inhibited the uptake of nateglinide by Caco-2 cells [19], cis-inhibition studies were performed using benzoic acid and salicylic acid. As shown in Table 1, both of them significantly reduced the uptake of nateglinide.…”