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Hyperammonaemia in V1a vasopressin receptor knockout mice caused by the promoted proteolysis and reduced intrahepatic blood volume
- Source :
- The Journal of Physiology. 581:1183-1192
- Publication Year :
- 2007
- Publisher :
- Wiley, 2007.
-
Abstract
- 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.
- Subjects :
- chemistry.chemical_classification
medicine.medical_specialty
medicine.diagnostic_test
Physiology
Catabolism
Proteolysis
Protein metabolism
Metabolic acidosis
Biology
medicine.disease
Amino acid
Protein catabolism
chemistry.chemical_compound
Endocrinology
chemistry
Gluconeogenesis
Internal medicine
medicine
Glucose homeostasis
Subjects
Details
- ISSN :
- 00223751
- Volume :
- 581
- Database :
- OpenAIRE
- Journal :
- The Journal of Physiology
- Accession number :
- edsair.doi...........377a0ff3c4a3e012294dec692b2f3e59