STZ TRANSPORT AND CYTOTOXICITY - SPECIFIC ENHANCEMENT IN GLUT2-EXPRESSING CELLS
STZ TRANSPORT AND CYTOTOXICITY - SPECIFIC ENHANCEMENT IN GLUT2-EXPRESSING CELLS
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DOI：
10.2337/diabetes.43.11.1326
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发表时间：
1994-11-01
期刊：
影响因子：
7.7
通讯作者：
NEWGARD, CB
中科院分区：
文献类型：
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作者：
SCHNEDL, WJ;FERBER, S;NEWGARD, CB
葡萄糖类似物链脲佐菌素（STZ）由于其相对特异的β细胞毒性作用，长期以来一直被用作制造实验性糖尿病的工具，但全身注射STZ导致β细胞破坏的机制尚不清楚。在目前的研究中，我们已经使用胰岛素瘤（BIN）和AtT-20ins细胞系工程GLUT 2或GLUT 1的过度表达，调查葡萄糖转运蛋白亚型介导的STZ细胞毒性的作用。通过将表达或缺乏GLUT2的RIN细胞植入无胸腺裸大鼠中来评价STZ的体内作用。该药物对表达GLUT 2的BIN细胞具有强效细胞毒性作用，但对缺乏GLUT 2表达的细胞无作用，如组织学分析和给药动物血糖水平测量所示。通过对GLUT 2表达和未转染的RIN细胞以及GLUT 2和GLUT 1过表达的AtT-20ins细胞进行体外分析，证实了STZ对GLUT 2表达细胞系的优先细胞毒性作用。与这些数据一致，只有表达GLUT2的RIN或AtT-20ins细胞有效转运STZ。我们得出结论，GLUT 2的表达是必需的STZ的神经内分泌细胞的有效杀伤，这种效果是相关的药物作为转运底物的GLUT 2，而不是GLUT 1的特异性识别。
The glucose analog streptozotocin (STZ) has long been used as a tool for creating experimental diabetes because of its relatively specific beta-cell cytotoxic effect, but the mechanism by which systemic injection of STZ causes beta-cell destruction is not well understood. In the current study, we have used insulinoma (BIN) and AtT-20ins cell lines engineered for overexpression of GLUT2 or GLUT1 to investigate the role of glucose transporter isoforms in mediating STZ cytotoxicity. The in vivo effects of STZ were evaluated by implantation of RIN cells expressing or lacking GLUT2 into athymic nude rats. The drug had a potent cytotoxic effect on BIN cells expressing GLUT2, but had no effect on cells lacking GLUT2 expression, as indicated by histological analysis and measurement of the blood glucose levels of treated animals. The preferential cytotoxic effect of STZ on GLUT2-expressing cell Lines was confirmed by in vitro analysis of GLUT2-expressing and untransfected RIN cells, as well as GLUT2- and GLUT1-overexpressing AtT-20ins cells. Consistent with these data, only GLUT2-expressing RIN or AtT-20ins cells transported STZ efficiently. We conclude that expression of GLUT2 is required for efficient killing of neuroendocrine cells by STZ, and this effect is related to specific recognition of the drug as a transported substrate by GLUT2 but not GLUT1.