Exposure to p,p'-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice.
Exposure to p,p'-dichlorodiphenyldichloroethylene (DDE) induces fasting hyperglycemia without insulin resistance in male C57BL/6H mice.
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DOI：
10.1016/j.tox.2014.02.004
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发表时间：
2014-06-05
期刊：
影响因子：
4.5
通讯作者：
Chambers, Janice E.
中科院分区：
文献类型：
--
作者：
Howell, George E., III;Meek, Edward;Kilic, Jessica;Mohns, Mariel;Mulligan, Charlee;Chambers, Janice E.
约占美国（US）的8.3%糖尿病患者中有确诊或未确诊的糖尿病患者。在所有糖尿病病例中，约90-95%的病例为2型糖尿病（T2 D）。虽然T2 D的确切原因仍然难以捉摸，但诱发因素包括年龄，体重，不良饮食和久坐的生活方式。直到最近，暴露于环境污染物与糖尿病发生之间的关系尚未被探索。然而，最近的流行病学研究表明，某些持久性有机污染物（POP），特别是有机氯农药的血清浓度升高与T2 D和胰岛素抵抗的患病率增加呈正相关。目前的研究试图调查这种关联是因果关系还是巧合。雄性C57 BL/6 H小鼠经口灌胃给予DDE（2.0 mg/kg或0.4 mg/kg）或溶媒（玉米油; 1 ml/kg）5天;在7天休息期后进行空腹血糖、葡萄糖耐量和胰岛素激发试验。与溶媒相比，暴露于DDE可引起显著的高血糖，并且这种高血糖效应在DDE给药停止后持续长达21天。溶剂和DDE给药动物之间的腹膜内葡萄糖耐量试验和胰岛素激发后肝脏、骨骼肌和脂肪组织中Akt的磷酸化相当。为了确定暴露于DDE对葡萄糖摄取的直接影响，在L 6肌管和3 T3-L1脂肪细胞中进行了DDE暴露后的体外葡萄糖摄取测定。总之，亚急性暴露于DDE确实会产生空腹高血糖，但这种空腹高血糖似乎不是由胰岛素抵抗介导的。因此，目前的研究表明，亚急性接触DDE确实会改变全身葡萄糖稳态，可能是糖尿病相关高血糖症发生的一个促成因素。
Approximately 8.3% of the United States (U.S.) population have either diagnosed or undiagnosed diabetes mellitus. Out of all the cases of diabetes mellitus, approximately 90–95% of these cases are type 2 diabetes mellitus (T2D). Although the exact cause of T2D remains elusive, predisposing factors include age, weight, poor diet, and a sedentary lifestyle. Until recently the association between exposure to environmental contaminants and the occurrence of diabetes had been unexplored. However, recent epidemiological studies have revealed that elevated serum concentrations of certain persistent organic pollutants (POPs), especially organochlorine pesticides, are positively associated with increased prevalence of T2D and insulin resistance. The current study seeks to investigate if this association is causative or coincidental. Male C57BL/6H mice were exposed to DDE (2.0 mg/kg or 0.4 mg/kg) or vehicle (corn oil; 1 ml/kg) for five days via oral gavage; fasting blood glucose, glucose tolerance, and insulin challenge tests were performed following a seven day resting period. Exposure to DDE caused significant hyperglycemia compared to vehicle and this hyperglycemic effect persisted for up to 21 days following cessation of DDE administration. Intraperitoneal glucose tolerance tests and phosphorylation of Akt in the liver, skeletal muscle, and adipose tissue following insulin challenge were comparable between vehicle and DDE treated animals. To determine the direct effect of exposure to DDE on glucose uptake, in vitro glucose uptake assays following DDE exposure were performed in L6 myotubules and 3T3-L1 adipocytes. In summary, subacute exposure to DDE does produce fasting hyperglycemia, but this fasting hyperglycemia does not appear to be mediated by insulin resistance. Thus, the current study reveals that subacute exposure to DDE does alter systemic glucose homeostasis and may be a contributing factor to the development of hyperglycemia associated with diabetes.
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影响因子：
7.1
作者：
Biro, Frank M.;Wien, Michelle
通讯作者：
Wien, Michelle
DOI：
10.1152/ajpendo.00072.2001
发表时间：
2002-03-01
影响因子：
5.1
作者：
Gregoire, FM;Zhang, Q;West, DB
通讯作者：
West, DB
DOI：
10.1152/ajpendo.90617.2008
发表时间：
2008-12-01
影响因子：
5.1
作者：
Andrikopoulos, Sofianos;Blair, Amy R.;Proietto, Joseph
通讯作者：
Proietto, Joseph
影响因子：
7.7
作者：
Davis RC;Castellani LW;Hosseini M;Ben-Zeev O;Mao HZ;Weinstein MM;Jung DY;Jun JY;Kim JK;Lusis AJ;Péterfy M
通讯作者：
Péterfy M
DOI：
10.1097/jom.0b013e31815f889b
发表时间：
2008-03-01
影响因子：
3.2
作者：
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通讯作者：
Pavuk, Marian