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.