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This Article Full Text Full Text (PDF) All Versions of this Article: 581/3/1183    most recent jphysiol.2007.129569v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiroyama, M. Articles by Tanoue, A. Search for Related Content PubMed PubMed Citation Articles by Hiroyama, M. Articles by Tanoue, A. Related Collections Renal and Endocrine

¹ Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan
² Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto 860-8556, Japan

An analysis of arginine-vasopressin (AVP) V1a receptor-deficient (V1aR–/–) mice revealed that glucose homeostasis and lipid metabolism were altered in the mutant mice. Here, we used V1aR–/– mice to investigate whether the deficiency of the V1a receptor, which led to altered insulin sensitivity, affected protein metabolism. The serum 3-methylhistidine levels were increased in V1aR–/– mice under feeding conditions, indicating that proteolysis was enhanced in muscle tissue from V1aR–/– mice. Furthermore, serum amino acid profiling revealed that the amino acid levels, including glycogenic and branched-chain amino acids, were reduced in V1aR–/– mice. In addition, an alanine-loading test showed that gluconeogenesis was enhanced in V1aR–/– mice. Blood ammonia, which is a by-product of amino acid catabolism, was two times higher in V1aR–/– mice without hepatopathy under the feeding and fasting conditions than in wild-type mice. Amino acid profiling also revealed that the amino acid pattern was not typical of a urea-cycle enzymatic disorder. An ammonia tolerance test and an indocyanine green elimination test showed that V1aR–/– mice had lower ammonia clearance due to a decreased intrahepatic circulating blood volume. Metabolic acidosis, including lactic- and keto-acidosis, was not observed in V1aR–/– mice. These results provide evidence that proteolysis promotes the production of glucose in the muscles of V1aR–/– mice and that hyperammonaemia is caused by promoted protein catabolism and reduced intrahepatic blood volume. Thus, our study with V1aR–/– mice indicates that AVP plays a physiological role via the V1a receptor in regulating both protein catabolism and glucose homeostasis.

(Received 30 January 2007; accepted after revision 16 March 2007; first published online 22 March 2007)
Corresponding author A. Tanoue: Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. Email: atanoue{at}nch.go.jp

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