Alterations in pancreatic islet function produced by carcinogenic nitrosamines in the Syrian hamster.
Exposure of hamsters to 5 daily doses of 20 mg/kg N-nitrosobis(2-oxopropyl)amine (BOP) or 76 mg/kg N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), resulted in reduced insulin secretion in freshly isolated pancreatic islets. These treatments also reduced plasma insulin and glucose levels, and were hepatotoxic. The inhibition of insulin secretion, however, was transient. Islets isolated from treated hamsters that were then placed in culture secreted elevated levels of insulin for many months. When cultured islets were directly exposed to the nitrosamines for 3 days, there was also a transient reduction of insulin secretion that was subsequently normalized after removal of the nitrosamine from the medium. These results show that BOP and HPOP modify beta-cell function both directly, and possibly indirectly, via damage to the liver. Furthermore, the lack of immediate inhibition of insulin secretion when islets were incubated in the presence of BOP or HPOP as well as glucose, suggests that the nitrosamines do not bind to the glucose receptor.
Zucker
P F
PF
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Canada.
Archer
M C
MC
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D006224:Cricetinae; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008099:Liver / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines / Q000633:toxicity*
D001786:Blood Glucose; D002273:Carcinogens; D007328:Insulin; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; C013624:N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine; D001219:Aspartate Aminotransferases