| Summary: | 碩士 === 國立臺灣大學 === 毒理學研究所 === 101 === Di(2-ethylhexyl) phthalate (DEHP) is widely used in PVC products, such as plastic toys, decoration materials, medical equipment, beauty products, chemicals and food packaging, as a plasticizer to increase the toughness and ductility of plastic products. Human exposure usually through food or water, inhalation, skin contact, medical practices and breastfeed. DEHP causes reproductive toxicity, neurotoxicity, allergies, DNA damage, chromosome damage and deletion and liver tumors, the International Center for Research on Cancer (IARC) as a Group 2B, which may be classified human carcinogen. The patients who often associated with multiple risk factors, such as hypertension, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol and obesity, called metabolic syndrome. Patients with metabolic syndrome have a higher risk of diabetes.According the reports, women with higher levels of phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. DEHP will reduce secretion of insulin in rats offspring, and it may create insulin resistance in adulthood, but its mechanism is still unclear. The aim of this study is to discuss the effects of DEHP on insulin function and blood glucose regulation.In this study, DEHP treatment of pancreatic beta-cell line (RIN-m5F) was increased insulin secretion, and expressed phosphor IRS-1, phosphor Akt and phosphor ERK. DEHP also increase phosphorylation of JNK, p38, it may the reason of DEHP caused beta-cell apoptosis.We observed that 12 weeks oral exposure of DEHP (10, 25 and 100 mg/kg/day) to 3 and 5 weeks old male mice, DEHP significantly increase blood sugar, decrease plasma insulin and islet area, elevation of serum triglyceride and effect of glucose intolerance. On the other hand, we also treat 100 mg/kg/day of DEHP to pregnant female mice, until both male and female pups were weaned on postnatal day (PND) 21, all the offspring’s plasma insulin and insulin resistant were significantly increase.In conclusion, these results indicate that DEHP increased insulin secretion, and expressed phosphor IRS-1, phosphor Akt and phosphor ERK, DEHP also increase phosphorylation of JNK, p38 and it may the reason of DEHP caused beta-cell apoptosis. Moreover, DEHP significantly increase blood sugar, decrease plasma insulin and islet area, elevation of serum triglyceride and effect of glucose intolerance. It is show long-term exposure of high doses DEHP would likely induce a high risk of metabolic syndrome.
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