Protection of B cells against the effect of alloxan.
Alloxan induces diabetes in laboratory animals through the destruction of the endocrine pancreatic B cells. The mechanism of alloxan toxicity is still obscure. This study was conducted to investigate the effects of superoxide dismutase (SOD) or reduced nicotinamide adenine dinucleotide (NADPH) treatment on the B cells in isolated rat islets prior to alloxan treatment. Islets were treated with SOD (1000 U) or 0.1 mM NADPH for 10 min followed by alloxan treatment (0.18 mg) for 5 min. Insulin secretion was studied in samples incubated for 60 min in media supplemented with glucose (1.8 mg/ml). Morphological examinations were conducted on fixed samples after the alloxan treatment. SOD significantly protected the islets from the cytotoxic effect of alloxan. Although alloxan decreased insulin secretion to 35% of the control, SOD increased this level to 73% of the control values. NADPH did not provide any protection to the islets. Insulin secretion from islets treated with NADPH and alloxan was not different from that after alloxan treatment alone. Morphological changes were observed in the islets treated with alloxan alone or alloxan in the presence of NADPH. Islets exhibited multiple cellular necrosis, marked degranulation and extensive vesiculation of the endoplasmic reticulum and Golgi complex. Mitochondrial enlargement with disrupted cristae and mitochondrial ruptures were prominent. However, islets treated with SOD and alloxan were similar to the control except for the enlarged mitochondria. The increased insulin secretion from islets treated with SOD and alloxan reinforces the free radical hypothesis of alloxan toxicity. The markedly enlarged mitochondria was one of the targets through which alloxan destroyed the B cells.
Abdel-Rahman
M S
MS
Department of Pharmacology/Toxicology, New Jersey Medical School, Newark 07103-2714.
Elrakhawy
F I
FI
Iskander
F A
FA
D000496:Alloxan / Q000633:toxicity*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008854:Microscopy, Electron; D009249:NADP / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology*
D007328:Insulin; D009249:NADP; D000496:Alloxan; D013482:Superoxide Dismutase