Lipopolysaccharide Induces Inhibition of Galactose Intestinal Transport in Rabbits <i>in vitro</i>

Abstract

Background/Aims: Previous studies from our laboratory have revealed impaired intestinal absorption of D-galactose in lipopolysaccharide-treated rabbits. The aim of the present work was to examine the effect of LPS on D-galactose intestinal absorption in vitro. Methods: D-galactose intestinal transport was assessed employing three techniques: sugar uptake in rings of everted jejunum, transepithelial flux in Ussing-type chambers and transport assays in brush border membrane vesicles. The level of expression of the Na⁺/D-galactose cotransporter (SGLT1) was analyzed by Western blot. Results: LPS decreased the mucosal D-galactose transport in rabbit jejunum but a preexposition to the endotoxin was required. LPS affected the Na⁺-dependent transport system by increasing the apparent Km value without affecting the Vmax. It also decreased the Na⁺, K⁺-ATPase activity. However, it did not inhibit neither the uptake of D-galactose by brush border membrane vesicles nor modified the SGLT1 protein levels in the brush border, suggesting an indirect endotoxin effect. This inhibitory effect, was reduced by selective inhibitors of Ca²⁺-calmodulin (W13), protein kinase C (GF 109203X), p38 mitogen-activated protein kinase (SB 203580), c-Jun N-terminal kinase (SP 600125) and mitogen extracellular kinase (U 0126). Conclusion: LPS inhibits the mucosal Na⁺-dependent D-galactose intestinal absorption and the Na⁺, K⁺-ATPase activity when it is added to the tissue. Intracellular processes related to protein kinases seem to be implicated in the endotoxin effect.

The Effects of Critical Illness on Intestinal Glucose Sensing, Transporters, and Absorption*

“…The mechanisms underlying reduced SGLT-1 and GLUT2 expression in the critically ill are uncertain, but are likely to include disease-induced changes in cellular signaling within the intestinal epithelium (31). In animals it is established that the activation of intestinal STR has the capacity to regulate levels and function of SGLT-1, and in rats, the translocation of GLUT2 to the apical membrane (10,12).…”

Downregulation of Mouse Intestinal Na+-coupled Glucose Transporter SGLT1 by Gum Arabic (Acacia Senegal)

“…Previous studies have revealed that SGLT1 may be subject to regulation of transcription [15], mRNA stability [16], transporter protein abundance in the plasma membrane [17], and transporter activity [18]. Factors modifying SGLT1 activity include carbohydraterich diet [19], adrenergic innervation [20], insulin [21], glucagon-like peptide 2 [22], cholecystokinin [17], insulinlike growth factors [23], cytosolic Na + [24] and lipopolysaccharides [25]. Moreover, SGLT1 activity is regulated by phosphatidylinositol (PI) 3 kinase [26], the phosphoinositide-dependent kinase 1 (PDK1) [27] as well as the serum-and glucocorticoid-regulated kinase isoforms SGK1 and SGK3 [14,28], kinases regulating the transport of a variety of nutrients and channels [14,[28][29][30][31][32][33].…”

From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol

“…How DON causes inhibition of SGLT1 and other nutrient transporters is unknown at present, this inhibition being possibly related either to non-specific effects such as protein synthesis inhibition or ATP depletion, or to specific modulation of the expression/membrane targeting/activity of the transporters. According to the second hypothesis, activation of MAP kinases in IEC by proinflammatory signals causes the inhibition of the activity of membrane inserted SGLT-1 without affecting its expression [106,107]. …”