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Am J Physiol Gastrointest Liver Physiol (June 2, 2005). doi:10.1152/ajpgi.00026.2005
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Submitted on January 24, 2005
Accepted on May 25, 2005

Intestinal-renal metabolism of L-citrulline and L-arginine following enteral or parenteral infusion of L-alanyl-L-[2,15N]glutamine or L-[2,15N]glutamine in mice

Petra G. Boelens1, Paul A.M. van Leeuwen1*, Cornelis H.C Dejong2, and Nicolaas E.P. Deutz2

1 Department of Surgery, VU University medical center, Amsterdam, The Netherlands
2 Department of Surgery, the University of Maastricht, Maastricht, The Netherlands

* To whom correspondence should be addressed. E-mail: pam.vleeuwen{at}vumc.nl.

Previously, we observed increased plasma arginine after glutamine-enriched diets, in combination with clinical benefits. GLN delivers nitrogen for arginine (ARG) synthesis and the present study was designed to quantify the inter-organ relations of exogenous L-GLN or glutamine-dipeptide, by enteral or parenteral route, contributing to intestinal citrulline (CIT) and renal de novo ARG synthesis in mice. To study this, we used a multi-catheterised mice model with Swiss mice (n=43) in the post-absorptive state. Stable isotopes were infused into the jugular vein or into the duodenum (per group either free L-[2,15N]GLN or dipeptide L-ALA-L-[2,15N]GLN, all with L-[ureido-13C- 2H2]CIT and L-[guanidino-15N2-2H2]ARG) to establish renal and intestinal arginine and citrulline metabolism. Blood flow was measured using 14C-para-aminohippuric acid (14CPAH). Net intestinal CIT release, renal uptake of CIT and net renal ARG efflux was found, assessed by A-V flux measurements. Quantitatively more de novo L-[2,15N]CIT was produced when free L-[2,15N]GLN was given than when L-ALA-L-[2,15N]GLN was given, while renal de novo L-[2,15N]arginine was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice. L-[2,15N]glutamine or dipeptide were both converted into de novo renal L- [2,15N]arginine, however, not all derived from intestinal L-[2,15N] citrulline production. In this model feeding route and form of glutamine did not influence de novo renal arginine production derived from glutamine.




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