Destruction of Pancreatic β-Cells by Transgenic Induction of Prostaglandin E2 in the Islets

Oshima, Hiroko; Taketo, Makoto Mark; Oshima, Masanobu

doi:10.1074/jbc.m602424200

Cited by 49 publications

(44 citation statements)

References 30 publications

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“…We have measured TNF-a protein levels in islets from fresh soyabean oil-or OFO-fed mice, but found no difference (data not shown). Since significantly higher levels of PGE 2 metabolites have been observed in the plasma and urine of OFO-fed rats (43) and increased PGE 2 expression in islets has been shown to result in the destruction of pancreatic islets (44) . The effect of oxidative stress, inflammation and apoptosis on b-cells and OFOinduced islet dysfunction awaits further study.…”

Section: Discussionmentioning

confidence: 99%

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

et al. 2010

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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 ...

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Section: Discussionmentioning

confidence: 99%

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

et al. 2010

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“…In addition, we could not exclude the possibility that the metabolic alteration in OFO-fed rats might partially be related to a compromised vitamin E status, since most of the vitamin E in the oil is destroyed during the frying process and the absorption and retention of this vitamin in tissues is reduced in rats fed a frying oil diet (Liu & Huang, 1995. Recently, Oshima et al (2006) showed that the increased prostaglandin E 2 expression in the islets resulted in the destruction of pancreatic beta cells. Since significantly higher prostaglandin E 2 metabolites in plasma and urine of OFO-fed rats have been observed in our previous studies (Huang, 2003), whether the glucose intolerance observed in the OFO-fed rodents is associated with an altered prostaglandin metabolism is under investigation.…”

Section: Discussionmentioning

confidence: 99%

A high oxidised frying oil content diet is less adipogenic, but induces glucose intolerance in rodents

et al. 2007

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Oxidised frying oil (OFO) and fish oil have been shown to be peroxisome proliferator-activated receptor (PPAR)a activators and their ingestion results in pleotropic peroxisome proliferator responses in rats. To examine the effect of dietary OFO on adiposity, four groups of weanling Sprague -Dawley rats were fed isoenergetically with, respectively, a low fat basal diet containing 5 g/100 g of fresh soybean oil (LSB) or a high fat diet containing 20 g/100 g of fresh soybean oil (HSB), OFO (HO) or fish oil (HF). The tissue mass, cell size and lipid/DNA ratio in the retroperitoneal fat pad and serum leptin levels were lowest in the HO group (P,0·05), indicating that dietary OFO has a greater anti-adipogenic action than dietary fish oil. However, a tendency to hyperglycaemia was observed in the HO group (P¼ 0·0528). To examine the effect of dietary OFO on glucose tolerance, three groups of rats and three groups of mice were fed, respectively, the LSB, HSB or HO diet, and an oral glucose tolerance test was performed. After oral glucose load, the area under the curve for blood glucose (AUC glu ) over 2 h was significantly higher, and that for serum insulin (AUC ins ) over 90 min was significantly lower, in the HO group than in the other two groups (P, 0·05). These results demonstrate that, in rats and mice, a high OFO diet is less adipogenic, but induces glucose intolerance.

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“…Pancreatic islets were isolated by a modified collagenase digestion method as described pre- (Zhang et al, 2001;Oshima et al, 2006). Anesthetized Ephx2(Ϫ/Ϫ) and Ephx2(ϩ/ϩ) mice were sacrificed by cervical dislocation.…”

Section: Methodsmentioning

confidence: 99%

Inhibition or Deletion of Soluble Epoxide Hydrolase Prevents Hyperglycemia, Promotes Insulin Secretion, and Reduces Islet Apoptosis

Luo

Chang

Zhou

et al. 2010

J Pharmacol Exp Ther

107

123

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Soluble epoxide hydrolase (sEH) is an enzyme involved in the metabolism of endogenous inflammatory and antiapoptotic mediators. However, the roles of sEH in diabetes and the pancreas are unknown. Our aims were to determine whether sEH is involved in the regulation of hyperglycemia in diabetic mice and to investigate the reasons for the regulation of insulin secretion by sEH deletion or inhibition in islets. We used two separate approaches, targeted disruption of Ephx2 gene [sEH knockout (KO)] and a selective inhibitor of sEH [trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB)], to assess the role of sEH in glucose and insulin homeostasis in streptozotocin (STZ) mice. We also examined the effects of sEH KO or t-AUCB on glucose-stimulated insulin secretion (GSIS) and intracellular calcium levels in islets. Hyperglycemia in STZ mice was prevented by both sEH KO and t-AUCB. In addition, STZ mice with sEH KO had improved glucose tolerance. More important, when insulin levels were assessed by hyperglycemic clamp study, sEH KO was found to promote insulin secretion. In addition, sEH KO and t-AUCB treatment augmented islet GSIS. Islets with sEH KO had a greater intracellular calcium influx when challenged with high glucose or KCl in the presence of diazoxide. Moreover, sEH KO reduced islet cell apoptosis in STZ mice. These results show not only that sEH KO and its inhibition prevent hyperglycemia in diabetes, but also that sEH KO enhances islet GSIS through the amplifying pathway and decreases islet cell apoptosis in diabetes.The prevalence of diabetes continues to increase. It is estimated that 225 million people are affected worldwide (Mazzone, 2009). Moreover, the diabetic population is subject to a high incidence of cardiovascular and renal diseases (Breyer et al., 2005;Mazzone, 2009). Diabetes is characterized by hyperglycemia related to abnormalities in the function of pancreatic ␤ cells. Because ␤-cell destruction and dysfunction are the central events in the development and progression of diabetes, the prevention of ␤-cell destruction and the improvement of ␤-cell function could be important strategies for controlling the advance of diabetes (Kahn et al., 2006;Donath et al., 2008).In pancreatic ␤ cells, glucose stimulates insulin secretion by activating the triggering and amplifying pathways (Henquin, 2000). In the triggering pathway, products of glucose metabolism enter the mitochondrial respiratory chain, which uses them to generate ATP. Increased ATP levels close the K ATP -sensitive channels, followed by membrane depolarization and opening of the voltage-sensitive Ca 2ϩ channels, which in turn increase intracellular Ca 2ϩ concentration and

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Destruction of Pancreatic β-Cells by Transgenic Induction of Prostaglandin E2 in the Islets

Cited by 49 publications

References 30 publications

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

Dietary oxidised frying oil causes oxidative damage of pancreatic islets and impairment of insulin secretion, effects associated with vitamin E deficiency

A high oxidised frying oil content diet is less adipogenic, but induces glucose intolerance in rodents

Inhibition or Deletion of Soluble Epoxide Hydrolase Prevents Hyperglycemia, Promotes Insulin Secretion, and Reduces Islet Apoptosis

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