Peschke E, Ebelt H, Brömme H J, Peschke D
Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Saale, Germany.
Cell Mol Life Sci. 2000 Jan 20;57(1):158-64. doi: 10.1007/s000180050505.
This study compares functional and morphological alterations caused by application of alloxan, streptozotocin, xanthine oxidase/hypoxanthine (generation of reactive oxygen species), or S-nitroso-N-acetyl-D,L-penicillamine (SNAP, liberation of nitric oxide) to isolated rat pancreatic islets in vitro. In perifusion experiments, membrane leakage--detected by non-stimulated insulin release--was found after application of all drugs, but showed a substance-specific time pattern. Twenty-four hours after application of the classical diabetogens (alloxan or streptozotocin), potassium chloride- and glucose-stimulated insulin secretion were markedly reduced, while a persistent reduction was observed neither after exposure to xanthine oxidase/hypoxanthine, nor to SNAP. Morphological analysis of the islets revealed that nearly all beta-cells were destroyed following alloxan or streptozotocin treatment, while the majority of beta-cells were configured regularly after application of xanthine oxidase/hypoxanthine or SNAP. Necrotic cells found after xanthine oxidase/hypoxanthine usually differed in morphology from those observed after application of the classical diabetogens. While the former cells were characterised by swollen nuclei, the latter had shrunken nuclei with irregular condensed chromatin. Apoptosis was found only following nitric oxide exposure. Due to these differences, it seems unlikely that alloxan, streptozotocin, xanthine oxidase/hypoxanthine, and nitrix oxide have a common major feature in their toxic action.
本研究比较了在体外对分离的大鼠胰岛应用四氧嘧啶、链脲佐菌素、黄嘌呤氧化酶/次黄嘌呤（产生活性氧）或S-亚硝基-N-乙酰-D,L-青霉胺（SNAP，释放一氧化氮）所引起的功能和形态学改变。在灌流实验中，通过非刺激状态下胰岛素释放检测到的膜渗漏在应用所有药物后均有发现，但呈现出物质特异性的时间模式。应用经典致糖尿病药物（四氧嘧啶或链脲佐菌素）24小时后，氯化钾和葡萄糖刺激的胰岛素分泌显著减少，而在暴露于黄嘌呤氧化酶/次黄嘌呤或SNAP后均未观察到持续减少。胰岛的形态学分析显示，四氧嘧啶或链脲佐菌素处理后几乎所有β细胞均被破坏，而应用黄嘌呤氧化酶/次黄嘌呤或SNAP后大多数β细胞形态正常。黄嘌呤氧化酶/次黄嘌呤处理后发现的坏死细胞形态通常与应用经典致糖尿病药物后观察到的不同。前者细胞的特征是细胞核肿胀，而后者细胞核皱缩，染色质凝聚不规则。仅在一氧化氮暴露后发现凋亡。由于这些差异，四氧嘧啶、链脲佐菌素、黄嘌呤氧化酶/次黄嘌呤和一氧化氮在其毒性作用中似乎不太可能有共同的主要特征。
