Intestinal phosphate absorption: The paracellular pathway predominates?

IMPACT STATEMENT: This review summarizes the work on transcellular intestinal phosphate absorption, arguing why this pathway is not the predominant pathway in humans consuming a "Western" diet. We then highlight the recent evidence which is strongly consistent with paracellular intestinal phosphate absorption mediating the bulk of intestinal phosphate absorption in humans.

[The regulation of Na+/H+ exchangers by Toll-like receptors under inflammation].

Toll-like receptors (TLRs) can be recognized and activated by different pathogen associated molecular patterns (PAMPs), which induce innate immune response and inflammation of the body. Na+/H+ exchangers (NHEs) not only play roles in the regulation of cellular pH and cell volume, maintenance of the cavity microenvironment and nutrients absorption, but also are related to cell proliferation, migration and apoptosis. The activity and membrane protein expression of NHEs are inhibited under the inflammation condition. It has been shown that the activation of TLR2 in colon epithelial cells can inhibit the activity of NHE1 through MyD88 independent pathway, which involves the recruitment of Src and the phosphorylation of PI3Ks. Other studies on intestinal macrophage showed long-term LPS stimulation can induce TLR4 activation through MyD88-dependent pathway (TLR4/MyD88/NF-κB) and induce inflammation and degeneration of intracellular NHE1, which leads to NHE1 activity inhibition. But short-term LPS exposure increases the activity and protein expression of NHE1. The activation of TLR5 increases the activity of NHE3. The activity and/or expression of NHE3 in intestinal macrophages in colitis patients and model animals were decreased. In renal tubular epithelial cells, basolateral LPS stimulation inhibits luminal NHE3 activation through TLR4/MyD88-dependent MAPK/ERK signaling pathway. And LPS stimulation on the lumen side activates TLR4/MyD88-dependent PI3K-AKT-mTOR signaling pathway, which results in the inhibition of NHE1 activity in basolateral side, and then affects the NHE3 function of the lumen side.

Increases in the expression of Na+ /H+ exchanger 1 and 3 are associated with insulin signalling in the ruminal epithelium.

Na+ /H+ exchanger (NHE), which catalyses the exchange of extracellular Na+ for intracellular H+ , is of importance in the maintenance of Na+ and pH homoeostasis for rumen epithelial cells. Studies in ruminants showed that high concentrate diets could increase the expression of NHE in ruminal epithelium. Results of recent studies further indicated that insulin, as an important hormone closely related to dietary concentrate, could enhance the expression of NHE. In this study, we have investigated the mechanisms of insulin regulating the expression of NHE in rumen epithelial cells and its potential role in dietary modulation of NHE expression in ruminal epithelium of cows. In primary culture, insulin increased phosphorylation of ERK 1/2 and AKT in rumen epithelial cells. However, this promotion was diminished by insulin receptor inhibitor. Insulin also stimulated NHE1 and NHE3 expression. But this increase was suppressed by insulin receptor inhibitor, ERK inhibitor and AKT inhibitor. In the present animal experiment, NHE1 and NHE3 expression increased in rumen epithelium of cows ingesting a high concentrate diet (HC, 60% concentrate), accompanied by increased insulin concentration in plasma, compared to those feeding a low concentrate diet (LC, 20% concentrate). Furthermore, the phosphorylation of ERK1/2 and AKT was higher in the rumen epithelium of the HC group than those in the LC group. Collectively, these results indicate that diet-dependent change of NHE1 and NHE3 abundance was mediated, at least in part, by plasma insulin through the ERK and AKT pathway.