title: Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats.
abstract: Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.
authors: a Department of Surgery , VU University Medical Center , Amsterdam , The Netherlands and Department of Surgery , Medical Center Alkmaar, Trial Center Holland Health , Alkmaar , The Netherlands.
authors: Nikki
authors: N
authors: Buijs
authors: Mechteld A R
authors: MA
authors: Vermeulen
authors: Viola B
authors: VB
authors: Weeda
authors: James R
authors: JR
authors: Bading
authors: Alexander P J
authors: AP
authors: Houdijk
authors: Paul A M
authors: PA
authors: van Leeuwen
mesh_terms: D000818:Animals; D001120:Arginine / Q000096:biosynthesis / Q000378:metabolism*; D002100:Cachexia / Q000139:chemically induced / Q000378:metabolism*; D004032:Diet; D005973:Glutamine / Q000008:administration & dosage*; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene; D010288:Parenteral Nutrition; D051381:Rats; D011916:Rats, Inbred F344; D012079:Renal Circulation / Q000502:physiology; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D005973:Glutamine; D008748:Methylcholanthrene; D001120:Arginine