Abstract
In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and Na+/K+-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na+/K+-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO.
Highlights
Na-glucose co-transport (SGLT1), found in the brush border membrane (BBM) of the absorptive villus cells is the most abundant Na-dependent nutrient transporter present in the mammalian small intestine
This study demonstrated that SGLT1 activity is significantly decreased in villus cells from SAMP1 mouse model ofmice chronicintestine, ileitis
The mechanism of lysine dihydrochloride (L-NIL) mediated restoration of decreased Na-glucose co-transport activity in ileal villus cells was by restoring the number of BBM SGLT1 protein to its normal levels
Summary
Na-glucose co-transport (SGLT1), found in the brush border membrane (BBM) of the absorptive villus cells is the most abundant Na-dependent nutrient transporter present in the mammalian small intestine. Since it is a secondary active transporter, Na+ /K+ -ATPase present in the basolateral membrane (BLM) of villus cells provides a favorable transcellular Na gradient required for its optimal activity [1]. SGLT1’s activity can be regulated in the villus cells at the level of BBM co-transporter and/or at the level of Na-extruding capacity of the cell. Preserved function of SGLT1 is the basis for the most efficacious and affordable treatment, oral rehydration solution, for the number one cause of infant mortality in the developing countries, namely diarrheal diseases.
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