REOXYGENATION INJURY AFFECTS ISOLATED ISLET RESPONSE TO FATTY-ACID STIMULATION

Hyperlipidemia is frequently associated with hyperinsulinemia, but bec ause the effects of fatty acids on insulin secretion in in vitro studi es using isolated perifused islets have mostly been described with sup raphysiological concentrations of fatty acids, it has remained uncerta in whether elevated lipid levels contribute to hyperinsulinemia by the ir direct stimulation of insulin secretion. In the present study, we h ave identified reoxygenation injury in isolated islet function as a co ntributing factor in the failure of physiological concentrations of fr ee fatty acids to stimulate insulin secretion in isolated perifused is lets, Reoxygenation of isolated islets is associated with the producti on of reactive oxygen species, which impair islet function. We have fo und that pretreatment of freshly isolated islets with the antioxidant: glutathione (GSH), as well as a 24-hour preculture of isolated islets under appropriate conditions, enhanced their sensitivity to fatty aci d stimulation. Copyright (C) 1998 by W.B. Saunders Company.