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.
Previously, we observed increased plasma arginine (ARG) concentrations after glutamine (GLN)-enriched diets, in combination with clinical benefits. GLN delivers nitrogen for ARG synthesis, and the present study was designed to quantify the interorgan relationship of exogenous L-GLN or GLN 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 multicatheterized mouse model with Swiss mice (n = 43) in the postabsorptive state. Stable isotopes were infused into the jugular vein or into the duodenum {per group either free L-[2,(15)N]GLN or dipeptide L-ALA-L-[2,(15)N]GLN, all with L-[ureido-(13)C-(2)H(2)]CIT and L-[guanidino-(15)N(2)-(2)H(2)]ARG} to establish renal and intestinal ARG and CIT metabolism. Blood flow was measured using (14)C-para-aminohippuric acid. Net intestinal CIT release, renal uptake of CIT, and net renal ARG efflux was found, as assessed by arteriovenous flux measurements. Quantitatively, more de novo L-[2,(15)N]CIT was produced when free L-[2,(15)N]GLN was given than when L-ALA-L-[2,(15)N]GLN was given, whereas renal de novo L-[2,(15)N]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that L-[2,(15)N]GLN or dipeptide were both converted into de novo renal L-[2,(15)N]ARG; however, not all was derived from intestinal L-[2,(15)N]CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.
Boelens
Petra G
PG
Dept. of Surgery, Vrije Universiteit University Medical Center, 1007 MB Amsterdam, The Netherlands.
van Leeuwen
Paul A M
PA
Dejong
Cornelis H C
CH
Deutz
Nicolaas E P
NE
D000465:Algorithms; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002956:Citrulline / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D006400:Hematocrit; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D017595:Renal Plasma Flow / Q000187:drug effects; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D004151:Dipeptides; D005973:Glutamine; D002956:Citrulline; D001120:Arginine; C054122:alanylglutamine; D010130:p-Aminohippuric Acid