Intestinal renal metabolism ofl-citrulline andl-arginine following enteral or parenteral infusion ofl-alanyl-l-[2,15N]glutamine orl-[2,15N]glutamine in mice

Abstract

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-[2,15N]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 ARG and CIT metabolism. Blood flow was measured using14C-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-[2,15N]CIT was produced when free l-[2,15N]GLN was given than when l-ALA-l-[2,15N]GLN was given, whereas renal de novo l-[2,15N]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that l-[2,15N]GLN or dipeptide were both converted into de novo renal l-[2,15N]ARG; however, not all was derived from intestinal l-[2,15N]CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.