Liu Su, Guo Xuechao, Wu Bing, Yu Haiyan, Zhang Xuxiang, Li Mei
State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
Sci Rep. 2014 Nov 4;4:6894. doi: 10.1038/srep06894.
Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic β-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic β-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.
砷作为2型糖尿病的潜在风险因素最近受到了关注。然而，砷在糖尿病发展过程中的作用尚不清楚。在本研究中，我们通过系统毒理学方法比较了无机砷（iAs）对正常小鼠和糖尿病小鼠的影响。虽然iAs暴露并未改变正常小鼠的糖耐量，但它导致了胰腺β细胞功能障碍，并增加了肝脏中的糖异生和氧化损伤。然而，iAs暴露使糖尿病小鼠的糖耐量恶化，这可能是由于糖异生增加和胰腺β细胞功能受损所致。有趣的是，基于胰岛素耐量试验，iAs暴露可通过激活正常个体和糖尿病个体中与葡萄糖摄取相关的基因和酶来提高胰岛素敏感性。我们的数据表明，iAs暴露可通过改变正常个体的脂质代谢、糖异生和胰岛素分泌而导致糖尿病前期效应，并通过这些过程使糖尿病个体的糖尿病效应恶化。胰岛素抵抗可能不是iAs导致糖尿病效应的原因，这表明iAs暴露致糖尿病效应的机制与传统风险因素（如肥胖）导致2型糖尿病的机制不同。
