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Glucocorticoids regulate intestinal glutamine synthetase gene expression in endotoxemia
P Sarantos1, A Abouhamze, R Chakrabarti
1Department of Surgery, University of Florida College of Medicine, Gainesville.
Archives of Surgery (Chicago, Ill. : 1960)
|January 1, 1994
Summary
During sepsis, gut glutamine uptake decreases. Glucocorticoids stimulate glutamine synthetase (GS) gene expression, supporting gut mucosal function when glutamine is scarce.
Area of Science:
- Gastroenterology
- Metabolic Regulation
- Sepsis Pathophysiology
Background:
- Glutamine is essential for maintaining gut mucosal metabolism and function.
- Intestinal glutamine uptake from the lumen and bloodstream is reduced during sepsis.
- Endogenous glutamine biosynthesis may compensate for decreased uptake.
Purpose of the Study:
- To investigate if endogenous mucosal glutamine biosynthesis increases during endotoxemia.
- To identify stress mediators regulating small intestinal glutamine synthetase (GS) activity.
- To understand the role of GS in de novo glutamine synthesis in the gut.
Main Methods:
- Rats were administered lipopolysaccharide (LPS) and various inhibitors (glucocorticoid antagonist, TNF antibody, prostaglandin inhibitor).
- Mucosal GS activity was measured in vivo.
- Cultured intestinal cells (Caco-2) were exposed to LPS and inflammatory mediators; GS activity and mRNA levels were quantified.
Main Results:
- LPS treatment significantly increased mucosal GS activity in rats.
- Glucocorticoid antagonism partially blocked the LPS-induced increase in GS activity.
- Dexamethasone, but not cytokines or prostaglandins, increased GS activity and mRNA in cultured cells, indicating direct glucocorticoid regulation.
Conclusions:
- Glucocorticoids directly stimulate GS gene expression in the intestinal mucosa.
- This hormonally mediated response supports de novo glutamine synthesis during sepsis.
- It compensates for reduced glutamine uptake from the gut lumen and blood.