Functional restoration of cultured mouse pancreatic islets after in vitro exposure to alloxan.
The molecular mechanisms behind the functional responses of the beta-cells after cytotoxic damage are still largely unknown. The aim of this study was to investigate to what extent the islet beta-cells are capable of repairing cellular injuries after acute treatment with increasing doses of alloxan. Isolated mouse pancreatic islets were exposed for 30 min. at 37 degrees to alloxan (1.0, 1.5 and 2.0 mM) or vehicle alone (controls). Immediately after alloxan exposure the islet glucose-stimulated insulin release was severely decreased, and there were morphological evidences of partial necrosis of the islets. After further six days in culture, there was a marked decrease in islet number in the groups of islets treated with 1.5 or 2.0 mM alloxan. However, the DNA and insulin contents of the remaining islets were similar to the values observed in cultured control islets. Furthermore, the insulin secretory response to glucose and the light microscopical appearance of these islets were largely restored on day 6. It is concluded that beta-cells surviving after an injury induced by alloxan may recover their functional capacity after an initial period of inhibited function.
Eizirik
D L
DL
Department of Medical Cell Biology, Uppsala University, Sweden.
Sandler
S
S
D000496:Alloxan / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D051379:Mice
D007328:Insulin; D000496:Alloxan; D004247:DNA