Borg L A
Acta Biol Med Ger. 1981;40(1):71-6.
To study some possible mechanisms responsible for the diabetogenic action of alloxan on the islets of Langerhans, islets isolated from normal mice were exposed to the drug at 4 degrees C. The low temperature employed during alloxan exposure minimized the degradation of the drug. Incubations performed at 37 degrees C after alloxan treatment of the islets in the cold showed that the drug had no effect on islet glucose utilization, whereas both islet glucose and leucine oxidation were inhibited. However, alloxan did not affect the islet activity of the plasma membrane bound enzyme adenylate cyclase (E.C. 4.6.1.1). From these and previous results it is concluded that the B-cytotoxicity of alloxan reflects an interaction with intracellular sites involved in the oxidative metabolism of the B-cell rather than with B-cell plasma membrane components. Furthermore, it was found that glucose, but not leucine or pyruvate, could protect against the inhibition of islet glucose oxidation. These findings could suggest that the B-cytotoxic action of the drug is prevented exclusively by hexoses.
为研究四氧嘧啶对胰岛产生致糖尿病作用的一些可能机制，将从正常小鼠分离出的胰岛在4℃下暴露于该药物。四氧嘧啶暴露期间采用的低温使药物降解减至最少。在低温下用四氧嘧啶处理胰岛后于37℃进行的孵育表明，该药物对胰岛葡萄糖利用无影响，而胰岛葡萄糖氧化和亮氨酸氧化均受到抑制。然而，四氧嘧啶并不影响质膜结合酶腺苷酸环化酶（E.C. 4.6.1.1）的胰岛活性。根据这些以及先前的结果得出结论，四氧嘧啶的β细胞毒性反映了其与参与β细胞氧化代谢的细胞内位点的相互作用，而非与β细胞质膜成分的相互作用。此外，发现葡萄糖而非亮氨酸或丙酮酸可防止胰岛葡萄糖氧化受到抑制。这些发现可能提示该药物的β细胞毒性作用仅由己糖预防。
