Corticosteroids reverse the inhibition of Na-glucose cotransport in the chronically inflamed rabbit ileum.
In a rabbit model of chronic ileal inflammation, we previously demonstrated inhibition of Na-glucose cotransport (SGLT-1). The mechanism of inhibition was secondary to a decrease in the number of cotransporters and not solely secondary to an inhibition of Na-K-ATPase or altered affinity for glucose. In this study, we determined the effect of methylprednisolone (MP) on SGLT-1 inhibition during chronic ileitis. Treatment with MP almost completely reversed the reduction in SGLT-1 in villus cells from the chronically inflamed ileum. MP also reversed the decrease in Na-K-ATPase activity in villus cells during chronic ileitis. However, MP treatment reversed the SGLT-1 inhibition in villus cell brush-border membrane vesicles from the inflamed ileum, which suggested an effect of MP at the level of the cotransporter itself. Kinetic studies demonstrated that the reversal of SGLT-1 inhibition by MP was secondary to an increase in the maximal velocity for glucose without a change in the affinity. Analysis of immunoreactive protein levels of the cotransporter demonstrated a restoration of the cotransporter numbers after MP treatment in the chronically inflamed ileum. Thus MP treatment alleviates SGLT-1 inhibition in the chronically inflamed ileum by increasing the number of cotransporters and not solely secondary to enhancing the activity of Na-K-ATPase or by altering the affinity for glucose.
Sundaram
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U
Division of Digestive Diseases, Departments of Medicine and Physiology, Ohio State University School of Medicine, Columbus, Ohio 43210, USA.
Coon
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S
Wisel
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S
West
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AB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002908:Chronic Disease; D007079:Ileitis / Q000378:metabolism* / Q000473:pathology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008775:Methylprednisolone / Q000494:pharmacology*; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase; D008775:Methylprednisolone