Thiazolidinediones (TZDs) have been suggested to act beneficially on pancreatic islet function and on beta-cell viability but data concerning direct effects on isolated islets are controversial. Therefore, we have examined parameters of pancreatic insulin and glucagon secretion and biosynthesis in TZD-exposed rat pancreatic islets under physiological glucose level conditions and under conditions of glucolipotoxicity. Primary rat islets were incubated for 2.5 h with or without troglitazone (10 microM) in 5.6 mM glucose (standard glucose levels) and 16.7 mM glucose (high glucose levels); a subgroup was additionally treated with oleate (200 microM) to simulate acute glucolipotoxicity. Insulin and glucagon secretion, intracellular content and their respective mRNAs were quantified. Newly synthesized insulin was determined by pulse-labeling experiments. Troglitazone reduced insulin secretion at standard and high glucose levels by about one-third (P

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