Lisofylline, a Novel Antiinflammatory Agent, Protects Pancreatic β-Cells from Proinflammatory Cytokine Damage by Promoting Mitochondrial Metabolism

Proinflammatory cytokine-mediated pancreatic β-cell dysfunction is a key pathological event in type I diabetes mellitus. Lisofylline (LSF), an anti-inflammatory agent, has been shown to protect pancreatic islets from IL-1β-induced inhibitory effects on insulin release. However, the mechanism of LSF action is not known. Increasing evidence suggests that the mitochondria play an important role in regulating the β-cell insulin release capacity and the control of cellular viability. To examine the direct effects of LSF on β-cells, insulin-secreting INS-1 cells were exposed to a combination of recombinant IL-1β, TNFα, and IFNγ with or without LSF for 18 h. Basal and glucose-stimulated static insulin release were measured using RIA. INS-1 cell viability was determined using in situ terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and LIVE/DEAD dual fluorescence labeling. To evaluate INS-1 mitochondrial function, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism, c...