title: Preferential reduction of insulin production in mouse pancreatic islets maintained in culture after streptozotocin exposure.
abstract: The ability of the pancreatic beta-cell to repair itself after a cytotoxic injury and reassume its functional activities may be a key issue in affording protection from insulin-dependent diabetes mellitus. The molecular mechanisms behind the functional responses of the beta-cell after cytotoxic damage are still largely unknown. The present study in an attempt to elucidate this issue. Mouse pancreatic islets were isolated with collagenase and, after overnight culture, exposed for 30 min at 37 C to 2.2 mM streptozotocin (SZ) or vehicle alone (controls). The islets were subsequently cultured for 6 days in medium RPMI-1640 plus 10% calf serum. After the culture they were subjected to light microscopical examinations or different functional tests during short term incubations. The SZ-treated islets showed markedly diminished insulin release after stimulation with the beta-cell nutrients glucose and leucine plus glutamine. Compounds known to increase intracellular cAMP [theophylline and (Bu)2-cAMP] were able to partially counteract the SZ-induced reduction of insulin release. Stimulation with arginine could also slightly restore the impaired insulin release. Glucose-stimulated oxygen uptake, proinsulin biosynthesis, and insulin and insulin mRNA contents were also decreased, with values at about 50% of the controls. However, the cellular contents of DNA and RNA and total protein biosynthesis rates were essentially normal. Besides mild degranulation in some islets, the morphological appearance of the SZ-treated islets did not reveal any obvious differences compared to the control islets. The present observations suggest that after a toxic injury there remains a population of partially damaged beta-cells, which are able to maintain most of their basal metabolic functions, but fail to maintain adequate insulin biosynthesis and release.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D011384:Proinsulin / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D012313:RNA; D004247:DNA; D011384:Proinsulin