Pulmonary biotransformation of insulin in rat and rabbit.
Pulmonary biotransformation of insulin in rat and rabbit.
复制标题
大鼠和兔体内胰岛素的肺部生物转化。
DOI：
10.1016/0024-3205(92)90313-e
复制
发表时间：
1992
期刊：
影响因子：
6.1
通讯作者：
Mitra,AK
中科院分区：
文献类型：
--
作者：
Liu,FY;Kildsig,DO;Mitra,AK
研究了胰岛素在家兔和大鼠肺匀浆中的体外生物降解。胰岛素可以在兔肺匀浆中被氨基肽酶依次代谢成两个初级片段。氨基酸序列为des-Phe-InsulinB1（代谢物I）和des-Phe-Val-InsulinB1−2（代谢物II）。然而，在大鼠肺匀浆中仅鉴定出前者代谢物（代谢物I）。兔肺匀浆的kvm值分别为0.29±0.14 mM和16.4±6.9μM/hr/mg蛋白，而含有微粒体和细胞质的兔肺制剂的kvm值分别为0.22±0.07 mM和17.9±5.4μM/hr/mg蛋白。与兔肺细胞质部分相关的kvm0分别为0.32±0.16 μ m /hr/mg蛋白和20.6±6.1μM/hr/mg蛋白。结果表明，肺氨肽酶可能是一种胞质酶。二聚体胰岛素在肺匀浆中的降解速度比六聚体胰岛素快，这是由于酶和胰岛素聚集物之间碰撞频率的差异。据报道，肺中的主要代谢物几乎保留了与胰岛素相同的生物活性，这表明胰岛素的肺输送途径不会对其降糖活性产生不利影响。
In vitro biodegradation of insulin in rabbit and rat lung homogenates was investigated. Insulin can be sequentially metabolized into two primary fragments in rabbit lung homogenate by an aminopeptidase. The amino acid sequences of the fragments were found to be the des-Phe-InsulinB1(Metabolite I) and des-Phe-Val-InsulinB1−2(Metabolite II). However, only the former metabolite (Metabolite I) was identified in the rat lung homogenate. The kmand Vmvalues associated with rabbit lung homogenate were 0.29 ± 0.14 mM and 16.4 ± 6.9μM/hr/mg protein, respectively, whereas those for a rabbit lung preparation containing both microsomes and cytosol were 0.22 ± 0.07 mM and 17.9 ± 5.4μM/hr/mg protein, respectively. The kmand Vmassociated with the cytosolic fraction of rabbit lung were 0.32 ± 0.16 and 20.6 ± 6.1μM/hr/mg protein, respectively. The results indicate that the lung aminopeptidase may be a cytosolic enzyme. The degradation of dimeric insulin in the lung homogenate was faster than that of hexameric insulin due to the difference in collision frequency between the enzyme and insulin aggregates. The major metabolites in the lungs reportedly retain almost the same bioactivity of insulin, suggesting that the pulmonary route of insulin delivery will not adversely affect its hypoglycemic activity.