Munday R, Ludwig K, Lenzen S
Ruakura Agricultural Research Centre, Hamilton, New Zealand.
J Endocrinol. 1993 Oct;139(1):153-63. doi: 10.1677/joe.0.1390153.
Alloxan causes diabetes in experimental animals through its ability to destroy the insulin-secreting B-cells of the pancreas. Alloxan is hydrophilic and chemically unstable; it is reactive toward thiols, undergoing redox cycling in the presence of glutathione and oxidizing protein-bound thiol groups, as reflected by inhibition of the thiol enzymes, hexokinase and glucokinase. It is apparently also selectively taken up by the GLUT-2 glucose transporter in the pancreatic B-cell membrane. In order to investigate which, if any, of these physicochemical properties are important in the toxic action of alloxan, we have examined seven N-alkyl substituted alloxan derivatives of various diabetogenic activity. Hydrophilicity was identified as a factor essential for diabetogenicity. Stability, rate of redox cycling and reactivity toward thiol groups were not correlated with diabetogenicity. Selective uptake by the GLUT-2 glucose transporter is not a prerequisite for the diabetogenicity of alloxan derivatives.
四氧嘧啶通过破坏胰腺中分泌胰岛素的β细胞的能力，在实验动物中引发糖尿病。四氧嘧啶具有亲水性且化学性质不稳定；它对硫醇具有反应性，在谷胱甘肽存在下进行氧化还原循环，并氧化与蛋白质结合的硫醇基团，这可通过硫醇酶己糖激酶和葡萄糖激酶的抑制反映出来。它显然也被胰腺β细胞膜中的GLUT - 2葡萄糖转运蛋白选择性摄取。为了研究这些物理化学性质中的哪些（如果有的话）在四氧嘧啶的毒性作用中很重要，我们检查了七种具有不同致糖尿病活性的N - 烷基取代四氧嘧啶衍生物。亲水性被确定为致糖尿病性的一个关键因素。稳定性、氧化还原循环速率和对硫醇基团的反应性与致糖尿病性无关。GLUT - 2葡萄糖转运蛋白的选择性摄取不是四氧嘧啶衍生物致糖尿病性的先决条件。
