The study of mechanism and approach to treatment for the hyper-ammonemia in the glutamate dehydrogenase abnormality

高胰岛素血症由于对GTP抑制具有严重的不敏感性而导致GDH活性的失调，并介导了胰岛素的无调节分泌。我们制作了一只转基因小鼠，用于阐明高氨血症的机制和开发治疗方法。肝脏、心脏、肾脏和脑的代谢分析表明，肝脏的脂肪酸代谢增强，α-氧-戊二酸的合成减少。作为高氨血症的发病机制，N-乙酰谷氨酸不会降低，氨基甲酰磷酸合成酶活性也不会降低。新的日本患者已经通过GDH分析被诊断出来。

Hyperinsulinism hyperammonemia causes dysregulation of GDH activity due to have severe insensitivity for GTP inhibition, and mediate the unregulated insulin secretion. We made a transgenic mouse for elucidation of mechanism of hyperammonemia and development of a therapy. Metabolom analysis in liver, heart, kidney, and brain indicated the enhancement of fatty acid metabolism and decreased synthesis of α-oxoglutarate in liver. As onset mechanism of hyperammonemia, there is not decrease of N-acetylglutamate, and carbamoyl phosphate synthetase activity may not decrease. The new Japanese patients have been diagnosed with GDH analysis.