caa a22 4500 47584484X CHVBK 20180406123911.0 cr unu---uuuuu 170329e20000101xx s 000 0 eng 10.1007/s000180050505 doi (NATIONALLICENCE)springer-10.1007/s000180050505 ‘Classical' and ‘new' diabetogens—comparison of their effects on isolated rat pancreatic islets in vitro [Elektronische Daten] [E. Peschke*, H. Ebelt, H.-J. Brömme, D. Peschke] Abstract.: 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 β-cells were destroyed following alloxan or streptozotocin treatment, while the majority of β-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 nitric oxide have a common major feature in their toxic action. Birkhäuser Verlag Basel,, 2000 Key words. Alloxan nationallicence streptozotocin nationallicence xanthine oxidase/hypoxanthine nationallicence SNAP nationallicence reactive oxygen species nationallicence Peschke* E. Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale (Germany), Fax +49 345 5571700, DE aut Ebelt H. Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale (Germany), Fax +49 345 5571700, DE aut Brömme H.-J Institute of Pathophysiology, Martin Luther University, Halle-Wittenberg (Germany), DE aut Peschke D. Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale (Germany), Fax +49 345 5571700, DE aut https://doi.org/10.1007/s000180050505 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s000180050505 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Peschke* E. Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale (Germany), Fax +49 345 5571700, DE aut NATIONALLICENCE 700 1- Ebelt H. Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale (Germany), Fax +49 345 5571700, DE aut NATIONALLICENCE 700 1- Brömme H.-J Institute of Pathophysiology, Martin Luther University, Halle-Wittenberg (Germany), DE aut NATIONALLICENCE 700 1- Peschke D. Institute of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Grosse Steinstrasse 52, D-06097 Halle/Saale (Germany), Fax +49 345 5571700, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer