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,N-15] GLN or dipeptide L-ALA-L-[2,N-15] GLN, all with L-[ureido(13)C-2H(2)] CIT and L-[guanidino-N-15(2)-H-2(2)] ARG} to establish renal and intestinal ARG and CIT metabolism. Blood flow was measured using C-14-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,N-15]CIT was produced when free L-[ 2,N-15] GLN was given than when L-ALA-L-[2,N-15] GLN was given, whereas renal de novo L-[2,N-15]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that L-[2,N-15] GLN or dipeptide were both converted into de novo renal L-[2,N-15] ARG; however, not all was derived from intestinal L-[2,N-15] CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.