Epidermal growth factor and insulin short‐term increase hPepT1‐mediated glycylsarcosine uptake in Caco‐2 cells

Nielsen, Carsten Uhd; Amstrup, Jan; Nielsen, Robert; Steffansen, Bente; Frøkjær, Sven; Brodin, Birger

doi:10.1046/j.1365-201x.2003.01113.x

Cited by 30 publications

(18 citation statements)

References 36 publications

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“…After 5 min of exposure of the basolateral membrane of Caco-2 cells to EGF, there was a dose-dependent increase in the apical uptake of Gly-Sar (38). The kinetic analysis showed an increase in the V max of Pept-1-mediated transport of Gly-Sar without any change in the K m .…”

Section: Egfmentioning

confidence: 82%

“…Insulin, in a physiological concentration, applied for 60 min to the basolateral membrane, significantly increased the V max of Pept-1-mediated Gly-Sar transport without any change in the K m . Other new information presented by this study (38) was that a change in the intracellular pH was not responsible for the effect of insulin.…”

Section: Insulinmentioning

confidence: 89%

“…However, under in vivo conditions, the circulating insulin could regulate peptide transport by its binding to its receptors that are located on the basolateral membrane of the intestinal mucosal cells. This question was not investigated in the above study (52) but recently was investigated by another laboratory (38). It was found that previous exposure of the apical membrane of Caco-2 cells to insulin had no influence on apical uptake of Gly-Sar, but the exposure of the basolateral membrane to insulin in a dose-dependent manner significantly increased this uptake.…”

Section: Insulinmentioning

confidence: 93%

“…The kinetic analysis showed an increase in the V max of Pept-1-mediated transport of Gly-Sar without any change in the K m . The short-term EGF treatment did not alter either the Pept-1 mRNA level or the intracellular pH (38). However, the actual mechanism of increased Pept-1 functional expression remained unclear.…”

Section: Egfmentioning

confidence: 98%

“…This paradox was resolved by an additional study (38) that investigated the effect of EGF on Pept-1 expression after Caco-2 cells were briefly (for 1 h) exposed to this hormone. The rationale for this study (38) included the results of previous studies that had shown the long-term treatment (several days or longer) of Caco-2 cells with EGF results in a decrease in a number of brush-border membrane proteins (14).…”

Section: Egfmentioning

confidence: 99%

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Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease

Adibi

2003

American Journal of Physiology-Gastrointestinal and Liver Physi

196

131

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The abundance of the oligopeptide transporter (Pept-1) in the brush-border membrane of the intestinal epithelium is the central mechanism for regulation of transport of products of protein digestion (dipeptides and tripeptides) and peptidomimetic drugs (for example, β-lactam antibiotics). Within the past few years, there has been substantial progress in identifying the factors controlling this regulation and the mechanisms of their actions. The purpose of this report is to review this progress. The studies of individual substrates and hormones in a human intestinal cell line (Caco-2) have shown that dipeptides, certain amino acids, insulin, and leptin increase and epidermal growth factor and triiodothyronine decrease the membrane population of Pept-1. In the case of dipeptides, epidermal growth factor, and thyroid hormone, there are parallel changes in the gene expression brought about by alteration of transcription and/or stability of Pept-1 mRNA. In contrast, the treatment with insulin and leptin does not induce any alteration in the Pept-1 gene expression, and the mechanism of increased protein expression appears to be increased trafficking from a preformed cytoplasmic pool to the apical membrane. In vivo studies in rats have shown modulation of protein and gene expressions of the intestinal oligopeptide transporter during the day and during development and in nutritional and metabolic alterations, such as high-protein diet, fasting, and diabetes. Patients with intestinal diseases, such as ulcerative colitis, Crohn's disease, and short-bowel syndrome, may have induction of the Pept-1 expression in their colon. Finally, pharmacological studies have shown that the expression of Pept-1 can be upregulated by agents such as 5 fluorouracil and downregulated by agents such as cyclosporine. In conclusion, the above studies have produced a wealth of new information on regulation of a key transporter in the intestine. This information may have useful applications in nutritional and pharmacological treatments, for example, in diabetic patients needing enteral nutrition or in ulcerative colitis patients needing the suppression of the intestinal inflammation.

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Section: Egfmentioning

confidence: 82%

Section: Insulinmentioning

confidence: 89%