| First Author | Hiroyama M | Year | 2007 |
| Journal | J Physiol | Volume | 581 |
| Issue | Pt 3 | Pages | 1183-92 |
| PubMed ID | 17379633 | Mgi Jnum | J:141059 |
| Mgi Id | MGI:3815293 | Doi | 10.1113/jphysiol.2007.129569 |
| Citation | Hiroyama M, et al. (2007) Hyperammonaemia in V1a vasopressin receptor knockout mice caused by the promoted proteolysis and reduced intrahepatic blood volume. J Physiol 581(Pt 3):1183-92 |
| abstractText | 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. |
