Reoxygenation injury affects isolated islet response to fatty acid stimulation

Hyperlipidemia is frequently associated with hyperinsulinemia, but because the effects of fatty acids on insulin secretion in in vitro studies using isolated perifused islets have mostly been described with supraphysiological concentrations of fatty acids, it has remained uncertain whether elevated lipid levels contribute to hyperinsulinemia by their direct stimulation of insulin secretion. In the present study, we have identified reoxygenation injury in isolated islet function as a contributing factor in the failure of physiological concentrations of free fatty acids to stimulate insulin secretion in isolated perifused islets. Reoxygenation of isolated islets is associated with the production of reactive oxygen species, which impair islet function. We have found 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 acid stimulation.