We previously reported that, in rodents, a diet with a high oxidised frying oil (OFO) content leads to glucose intolerance associated with a reduction in insulin secretion. The present study aimed at investigating the impairment of pancreatic islets caused by dietary OFO. C57BL/6J mice were divided into three groups to receive a low-fat basal diet containing 5 g/100 g of fresh soyabean oil (LF group) or a high-fat diet containing 20 g/100 g of either fresh soyabean oil (HF group) or OFO (HO group). After 8 weeks, mice in the HO group showed glucose intolerance and hypoinsulinaemia, and their islets showed impaired glucose-stimulated insulin secretion (P,0·05; HO group v. LF and HF groups). Significantly higher oxidative stress and a lower mitochondrial membrane potential were observed in the islets in the HO group compared with the LF and HF groups. Immunoblots showed that the reduction in insulin levels in HO islets was associated with activation of the c-Jun NH 2 -terminal kinase and a reduction in levels of pancreatic and duodenal homeobox factor-1. In a second study, when dietary OFO-induced tissue vitamin E depletion was prevented by large-dose vitamin E supplementation (500 IU(1·06 mmol all-rac-a-tocopherol acetate)/kg diet; HO þ E group), the OFO-mediated reduction in islet size and impairment of glucose tolerance and insulin secretion were significantly attenuated (P, 0·05; HO group v. HO þ E group). We conclude that a high level of dietary OFO ingestion impairs glucose metabolism by causing oxidative damage and compromising insulin secretion in pancreatic islets, and that these effects can be prevented by vitamin E supplementation.Key words: Oxidised frying oil: Glucose-stimulated insulin secretion: Vitamin E: Pancreatic and duodenal homeobox factor-1: c-Jun NH 2 -terminal kinase Deep-frying is a common cooking practice, and the safety of oxidised frying oil (OFO) ingested with fried food is a concern. During the deep-frying process, a series of reactions, including auto-oxidation, thermal oxidation, polymerisation, cyclisation and fission, occur in the frying oil (1) . Generally, OFO prepared using normal cooking practices as part of a nutritionally balanced diet is regarded as safe due to the induction of detoxifying cytochrome P450 enzymes and the limited absorption of toxic polymers produced during the deep-frying process (2,3) . However, animal studies have revealed that some nutritional and metabolic effects related to OFO ingestion are noteworthy.We (4 -6) and others (7,8) have shown that, in rats and mice, OFO ingestion can influence lipid metabolism through the activation of PPARa in the liver, leading to increased fatty acid catabolism. Paradoxically, impairment of glucose metabolism, i.e. glucose intolerance, is observed in OFO-fed rodents (9) . When OFO-induced effects were compared with conjugated linoleic acid-induced lipodystrophic diabetes in mice, we found that, although both are characterised by body fat loss and glucose intolerance, OFO-mediated glucose intolerance is due to ...