Extracellular Glucose Concentration Alters Functional Activity of the Intestinal Oligopeptide Transporter (PepT-1) in Caco-2 Cells

D'Souza, Vanessa M.; Buckley, Donna J.; Buckley, Arthur R.; Pauletti, Giovanni M.

doi:10.1002/jps.10325

Cited by 18 publications

(22 citation statements)

References 35 publications

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“…Altogether, these results suggest that high extracellular glucose concentration affects hOCT3 mRNA transcription and protein activity levels in Caco-2 cells. Similarly, it was previously demonstrated that Caco-2 cells maintained in a 25 mM glucose medium, has a decreased PepT-1 transport activity (D'Souza et al 2003). According to these authors, an oxidative pathway seems to be responsible for this effect.…”

Section: Discussionmentioning

confidence: 83%

Impact of culture media glucose levels on the intestinal uptake of organic cations

et al. 2010

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There are several data concerning transporters expression and/or regulation in cell lines maintained in different conditions, such as medium glucose concentration. This work aimed to evaluate the influence of two different extracellular glucose concentrations, commonly used in culture media, on the intestinal absorption of organic cations. Thus, the effect of 5.5 mM glucose and 25 mM glucose (HG) in culture media, was studied on [(3)H]-MPP(+) (1-methyl-4-phenylpyridinium iodide) uptake in Caco-2 cells. Expression of human organic cation transporter type 1 (hOCT1) and human organic cation transporter type 3 (hOCT3) was investigated in cells cultured at both glucose concentrations. [(3)H]-MPP(+) uptake, as well as its affinity for the transporter, were significantly decreased in HG cells. Moreover, hOCT3 mRNA levels were reduced in HG cells. Functional confirmation of this result was made using hOCT3 inhibitors. In conclusion, maintenance of Caco-2 cells (commonly used in several in vitro studies on membrane transport) in HG conditions affects organic cation transport at the intestinal level. Hence, results obtained in these conditions must be analysed with great care, since extracellular glucose levels may originate changes in organic cation nutrient and drug bioavailability.

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Section: Discussionmentioning

confidence: 83%

Impact of culture media glucose levels on the intestinal uptake of organic cations

et al. 2010

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“…In this case, other factors must be taken into consideration, such as the transporter redox state. According to DÕSouza et al [24], who studied the activity of PepT-1 transporter in Caco-2 cells, the variations in the transporter redox state can be a mechanism able to regulate its activity. In fact, the results achieved in the experiments involving PAO, DTNB and DTT reinforce the hypothesis under consideration.…”

Section: Discussionmentioning

confidence: 99%

Modulation of MPP⁺ uptake by procyanidins in Caco‐2 cells: Involvement of oxidation/reduction reactions

et al. 2005

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It is becoming increasingly evident that the absorption of certain nutrients and drugs and their effects are largely influenced by the concomitant ingestion of other substances. As various xeno-and endobiotics belong to the class of organic cations, the aim of this work was to study the modulation of the intestinal apical uptake of organic cations by diet procyanidins.Five procyanidin fractions with different structural complexity were obtained after fractionation of a grape seed extract. The effect of these compounds on 1-methyl-4-phenylpyridinium (MPP + ) uptake was evaluated in Caco-2 cells. Apical uptake of 3 H-MPP + by Caco-2 cells was increased by a 60 min exposure to 600 lg ml À1 of procyanidin fractions, that increase being positively related with procyanidins structural complexity. It was verified that 3 H-MPP + uptake increased with preincubation time. It was speculated that procyanidins were oxidized during preincubation, this change could interfered with transport activity. Tested oxidizing agents showed that the redox state of the transporter could affect its activity. Additionally, trans-stimulation experiments showed that catechin and fraction I (the simpler fraction) can use the same transporter as MPP + . The results are compatible with the hypothesis of these compounds being competitive inhibitors of MPP + transport. In conclusion, procyanidins are capable to modulate MPP + apical uptake in Caco-2 cells, this transport being most probably modulated through oxidation-reduction phenomena. Interactions between these compounds and drugs present in the diet may affect their absorption and bioavailability. Both the concentration and complexity of the procyanidin compounds should be taken into account in medical practice.

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“…To confirm the cellular redox state involvement, both the effects of oxidant and reducing agents on the transport were tested (41) . The results obtained with these compounds confirmed that intra-and extracellular oxidation status interferes with the transport.…”

Section: H-mppmentioning

confidence: 99%

Effect of polyphenols on the intestinal and placental transport of some bioactive compounds

2010

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Polyphenols are a group of widely distributed phytochemicals present in most foods of vegetable origin. A growing number of biological effects have been attributed to these molecules in the past few years and only recently has their interference with the transport capacity of epithelial barriers received attention. This review will present data obtained concerning the effect of polyphenols upon the transport of some compounds (organic cations, glucose and the vitamins thiamin and folic acid) at the intestinal and placental barriers. Important conclusions can be drawn: (i) different classes of polyphenols affect transport of these bioactive compounds at the intestinal epithelia and the placenta; (ii) different compounds belonging to the same phenolic family often possess opposite effects upon transport of a given molecule; (iii) the acute and chronic/short-term and long-term exposures to polyphenols do not produce parallel results and, therefore, care should be taken when extrapolating results; (iv) the effect of polyphenolics in combination may be very different from the expected ones taking into account the effect of each of these compounds alone, and so care should be taken when speculating on the effect of a drink based on the effect of one component only; (v) care should be taken in drawing conclusions for alcoholic beverages from results obtained with ethanol alone. Although most of the data reviewed in the present paper refer to in vitro experiments with cell-culture systems, these studies raise a concern about possible changes in the bioavailability of substrates upon concomitant ingestion of polyphenols.

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Extracellular Glucose Concentration Alters Functional Activity of the Intestinal Oligopeptide Transporter (PepT-1) in Caco-2 Cells

Cited by 18 publications

References 35 publications

Impact of culture media glucose levels on the intestinal uptake of organic cations

Impact of culture media glucose levels on the intestinal uptake of organic cations

Modulation of MPP⁺ uptake by procyanidins in Caco‐2 cells: Involvement of oxidation/reduction reactions

Effect of polyphenols on the intestinal and placental transport of some bioactive compounds

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Extracellular Glucose Concentration Alters Functional Activity of the Intestinal Oligopeptide Transporter (PepT-1) in Caco-2 Cells

Cited by 18 publications

References 35 publications

Impact of culture media glucose levels on the intestinal uptake of organic cations

Impact of culture media glucose levels on the intestinal uptake of organic cations

Modulation of MPP+ uptake by procyanidins in Caco‐2 cells: Involvement of oxidation/reduction reactions

Effect of polyphenols on the intestinal and placental transport of some bioactive compounds

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Product

Resources

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Modulation of MPP⁺ uptake by procyanidins in Caco‐2 cells: Involvement of oxidation/reduction reactions