Department of Nutrition, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina 27599‑7461, USA.
Environ Health Perspect. 2011 Aug;119(8):1104-9. doi: 10.1289/ehp.1003324. Epub 2011 May 18.
Type 2 diabetes is characterized by glucose intolerance and insulin resistance. Obesity is the leading cause of type 2 diabetes. Growing evidence suggests that chronic exposure to inorganic arsenic (iAs) also produces symptoms consistent with diabetes. Thus, iAs exposure may further increase the risk of diabetes in obese individuals.
Our goal was to characterize diabetogenic effects of iAs exposure and high-fat diet (HFD) in weaned C57BL/6 mice.
Mice were fed HFD or low-fat diet (LFD) while exposed to iAs in drinking water (25 or 50 ppm As) for 20 weeks; control HFD and LFD mice drank deionized water. Body mass and adiposity were monitored throughout the study. We measured glucose and insulin levels in fasting blood and in blood collected during oral glucose tolerance tests (OGTT) to evaluate the diabetogenic effects of the treatment.
Control mice fed HFD accumulated more fat, had higher fasting blood glucose, and were more insulin resistant than were control LFD mice. However, these diabetes indicators decreased with iAs intake in a dose-dependent manner. OGTT showed impaired glucose tolerance for both control and iAs-treated HFD mice compared with respective LFD mice. Notably, glucose intolerance was more pronounced in HFD mice treated with iAs despite a significant decrease in adiposity, fasting blood glucose, and insulin resistance.
Our data suggest that iAs exposure acts synergistically with HFD-induced obesity in producing glucose intolerance. However, mechanisms of the diabetogenic effects of iAs exposure may differ from the mechanisms associated with the obesity-induced type 2 diabetes.
2 型糖尿病的特征是葡萄糖耐量降低和胰岛素抵抗。肥胖是 2 型糖尿病的主要原因。越来越多的证据表明，慢性接触无机砷（iAs）也会产生与糖尿病一致的症状。因此，iAs 暴露可能会进一步增加肥胖个体患糖尿病的风险。
我们的目标是描述 iAs 暴露和高脂肪饮食（HFD）对断奶 C57BL/6 小鼠的致糖尿病作用。
在饮用水中（25 或 50ppmAs）暴露于 iAs 的同时，将小鼠喂以 HFD 或低脂饮食（LFD）20 周；对照 HFD 和 LFD 小鼠饮用去离子水。在整个研究过程中监测体重和肥胖程度。我们测量了空腹和口服葡萄糖耐量试验（OGTT）期间采集的血液中的葡萄糖和胰岛素水平，以评估治疗的致糖尿病作用。
喂食 HFD 的对照小鼠比喂食 LFD 的对照小鼠积累了更多的脂肪，空腹血糖更高，胰岛素抵抗更严重。然而，这些糖尿病指标随 iAs 摄入量呈剂量依赖性降低。OGTT 显示，与相应的 LFD 小鼠相比，对照和 iAs 处理的 HFD 小鼠的葡萄糖耐量受损。值得注意的是，尽管肥胖程度、空腹血糖和胰岛素抵抗显著降低，但 iAs 处理的 HFD 小鼠的葡萄糖不耐受更为明显。
我们的数据表明，iAs 暴露与 HFD 诱导的肥胖协同作用导致葡萄糖耐量降低。然而，iAs 暴露致糖尿病的机制可能与肥胖引起的 2 型糖尿病相关的机制不同。
