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1、Why Should a Single Nutrient Glutamine - Improve OutcomeThe Glutamine and Glutamine-dipeptide storyNarrated by Peter FRST MD, PhD University Bonn Institute Nutritional ScienceBeijing, February 29, 2004A Piece of History1886 - A newly discovered substance found in the proteins from lupine and almond
2、(conglutin)Ritthausen J fr Praktische Chemie 1883 The first descriptionSchulze main substrate for renal ammoniagenesis (regulation of acid-base balance) Nitrogen transporter between tissues and regulator of amino acid homeostasis The major metabolic fuel for the mucosa and rapidly proliferating cell
3、s (immune system) Bergstrm et al. 1974, Meister 1983,Windmueller 1982, Souba 1991, Newsholme 1990Glutamine : A key substrate for the splanchnic bed The splanchnic bed regulates interorgan glutamine metabolism in normal and catabolic states Glutamine is essential for mucosal turnover and function Glu
4、tamine plays an important role in maintaining pancreatic function and supporting the immune systemW.W.Souba, 1991Glutamine Functions in Metabolism Precursor for glutathione synthesis Promoter of cellular hydration Attenuates insulin resistance Cardio-protective and rescue agentGlutamine and Glutathi
5、one glutamineGlu-Cys-Glyglutamic acidGlutamine and Glutathione In experimental studies supplemental glutamine preserves hepatic and intestinal mucosal stores of glutathione and maintains plasma concentrations.Hong et al. 1992; Harward et al. 1994; Yu et al. 1996; Denno et al. 1996 Experimental feedi
6、ng with glutamine results in considerable increase in its gut fractional uptake and a marked increase in intestinal GSH fractional release. Increased intestinal GSH productionCao et al. 1998Glutamine and Glutathione Combined therapy employing vitamin E and glutamine reversed the clinical and biochem
7、ical signs of severe hepatic dysfunction in VOD Total serum bilirubin concentration has normalized (33 mg% 2.4 mg%) Ascites and pedal edema (23 L) have resolvedNattakom et al. 1995 Current confirmatory reports with similar resultsBrown et al. 1998; Goringe et al. 1998Glutamine and Glutathione Surgic
8、al trauma and critical illness are associated with decreased concentrations of muscle glutathione, 40% and 60%, respectively. The decreased ratio GSH to GSSG suggests oxidative stress in this tissue. The low contents of glutathione were accompanied by intracellular glutamine depletion; 50% and 70%,
9、respectively.Luo et al. 1996; Hammarqvist et al. 1997Sufficient supply of glutamine ? There is a major demand on supply for the production of glutathione (GSH). Low intracellular glutamine levels correlate with depleted GSH pools. Hammarqvist et al., Crit Care Med, 25, 78, 1997 Wernerman et al., Pro
10、c Nutr Soc, 58, 677, 1999 Luo, 1999Glutamine and GlutathioneCurrent reportProvision of parenteral glutamine dipeptide attenuates post-traumatic glutathione depletion in human muscleFlring et al , Clin Sci 2003, 104: 275 - 282Glutamine Functions in Metabolism Precursor for glutathione synthesis Promo
11、ter of cellular hydration Attenuates insulin resistance Cardio-protective and rescue agentGlutamine and Cellular Hydration Increase in cellular hydration (swelling)- anabolic proliferative signal Decrease in cellular hydration (shrinkage)- catabolic anti proliferativeChanges in cellular hydration li
12、nk muscle glutamine content with protein turnover and because of the large muscle mass, with the N -balanceMuscle-cell water content and N-balance reveal an inverse correlationHusinger et al 1993 LancetGlutamine and Cellular HydrationA=Healthy subjects(17), B=Liver Tumors(5), C =Polytrauma day2, D=
13、Polytrauma 9day(11)E=Acute necrotizing pancreatit(6), F=Burns(4) Husinger et al 1993 LancetGlutamine and Cellular HydrationConcentrative uptake of Glutamine into muscle and liver cells increase cellular hydration trigger an anabolic signal Parenteral glutamine nutrition may improve cellular hydratio
14、n state thereby modify or reverse catabolic changes A consistent clinical observation: glutamine enriched parenteral feeding attenuates the expansion of extracellular waterScheltinga et al 1991; Ziegler et al 1992; Jiang et al 1999; Schloerb Morlion et al 1998Glutamine Functions in Metabolism Precur
15、sor for glutathione synthesis Promoter of cellular hydration Attenuates insulin resistance Cardio-protective and rescue agentGlutamine and HyperglycemiaHyperglycemia during critical illness a highly pertinent issue.van den Berghe et al 2001; Martinez-Riquelme Borel et al 1998Glutamine dipeptide supp
16、lemented critically ill patients revealed less hyperglycemia than control patients and in multi-trauma patients intravenous glutamine dipeptide nutrition enhanced insulin mediated glucose disposal.Clinical studies: Dechelotte et al 2002; Bakalar et al 2003Glutamine Functions in Metabolism Precursor for glutathione synthesis Promoter of c
