四氧嘧啶对胰腺β细胞选择性毒性的决定因素。
Determinants of the selective toxicity of alloxan to the pancreatic B cell.
作者信息
Malaisse W J, Malaisse-Lagae F, Sener A, Pipeleers D G
出版信息
Proc Natl Acad Sci U S A. 1982 Feb;79(3):927-30. doi: 10.1073/pnas.79.3.927.
Abstract
The diabetogenic agent alloxan exerts a preferential cytotoxic effect on the pancreatic B cell. The determinants of such a tissue specificity were investigated. Alloxan accumulated rapidly in liver and pancreatic islets but much more slowly in muscle. The activity of glutathione peroxidase and the resistance to exogenous peroxide were approximately 20 times higher in liver and kidney than in islets, intermediate values being found in exocrine pancreas and muscle. These findings suggest that the selective cytotoxicity of alloxan to the pancreatic B cell is attributable to the conjunction of two features: a rapid cellular uptake of the drug and an exquisite sensitivity of the B cell to peroxide.
摘要
致糖尿病药物四氧嘧啶对胰腺β细胞具有优先细胞毒性作用。对这种组织特异性的决定因素进行了研究。四氧嘧啶在肝脏和胰岛中迅速蓄积，但在肌肉中蓄积得慢得多。肝脏和肾脏中谷胱甘肽过氧化物酶的活性以及对外源过氧化物的抗性比胰岛中高约20倍，在外分泌胰腺和肌肉中发现的是中间值。这些发现表明，四氧嘧啶对胰腺β细胞的选择性细胞毒性可归因于两个特征的结合：药物的快速细胞摄取和β细胞对过氧化物的高度敏感性。
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