Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signalling in HepG2 cells and C57BL/6J mice
Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signalling in HepG2 cells and C57BL/6J mice
复制标题
DOI：
10.1007/s00125-011-2333-z
复制
发表时间：
2012-01-01
期刊：
影响因子：
8.2
通讯作者：
Tobacman, J. K.
中科院分区：
文献类型：
--
作者：
Bhattacharyya, S.;O-Sullivan, I.;Tobacman, J. K.
目的/假设本研究的目的是确定常见食品添加剂角叉菜胶（E407）对小鼠模型和人类肝细胞中葡萄糖耐量、胰岛素敏感性和胰岛素信号传导的影响，因为已知角叉菜胶通过与toll样受体（TLR）4相互作用引起炎症，而TLR 4与糖尿病炎症有关。方法在C57BL/6J雄性小鼠的饮水中加入10 mg/l的卡拉胶，分别进行葡萄糖耐量试验（GTT）、胰岛素耐量试验（ITT）和死前腹腔注射胰岛素。HepG2细胞暴露于卡拉胶（1 mg/l × 24 h）和胰岛素。western blotting和ELISA检测磷酸(Ser473)-蛋白激酶B （Akt）、磷酸(Ser307)-IRS1、磷酸肌肽3-激酶（PI3K）活性和磷酸(Ser32)- κ B抑制剂（I κ B α）水平。结果与未处理的对照组相比，经角叉菜胶处理的12周龄小鼠糖耐量在所有时间点均显著降低（n = 12; p < 0.0001）。在GTT期间服用葡萄糖后30分钟的基线胰岛素和胰岛素水平在卡拉胶治疗后显着升高。在ITT期间，对照组的血糖水平下降了80%以上，但用卡拉胶治疗的小鼠没有下降。卡拉胶暴露完全抑制胰岛素诱导的小鼠肝脏和人HepG2细胞中磷酸-(Ser473)- akt和PI3K活性的升高。卡拉胶增加磷酸(Ser307)-IRS1水平，当卡拉胶诱导的炎症被抑制时，这种水平被阻断。结论本文首次报道了卡拉胶对糖耐量的影响，表明卡拉胶在小鼠肝脏和人HepG2细胞中损害糖耐量，增加胰岛素抵抗，抑制胰岛素信号传导。这些影响可能是由卡拉胶引起的炎症引起的。研究结果表明，摄入的角叉菜胶有结肠外的表现，并表明人类饮食中的角叉菜胶可能有助于糖尿病的发展。
Aims/hypothesis The aim of this study was to determine the impact of the common food additive carrageenan (E407) on glucose tolerance, insulin sensitivity and insulin signalling in a mouse model and human hepatic cells, since carrageenan is known to cause inflammation through interaction with toll-like receptor (TLR)4, which is associated with inflammation in diabetes.Methods Male C57BL/6J mice were given carrageenan (10 mg/l) in their drinking water, and underwent a glucose tolerance test (GTT), an insulin tolerance test (ITT) and an ante-mortem intraperitoneal insulin injection. HepG2 cells were exposed to carrageenan (1 mg/l x 24 h) and insulin. Levels of phospho(Ser473)-protein kinase B (Akt), phospho(Ser307)-IRS1, phosphoinositide 3-kinase (PI3K) activity and phospho(Ser32)-inhibitor of kappa B (I kappa B alpha) were determined by western blotting and ELISA.Results Glucose tolerance was significantly impaired in carrageenan-treated 12-week-old mice compared with untreated controls at all time points (n = 12; p < 0.0001). Baseline insulin and insulin levels at 30 min after taking glucose during the GTT were significantly higher following carrageenan treatment. During the ITT, glucose levels declined by more than 80% in controls, but not in carrageenan-treated mice. Carrageenan exposure completely inhibited insulin-induced increases in phospho-(Ser473)-Akt and PI3K activity in vivo in mouse liver and in human HepG2 cells. Carrageenan increased phospho(Ser307)-IRS1 levels, and this was blocked when carrageenan-induced inflammation was inhibited.Conclusion This is the first report of the impact of carrageenan on glucose tolerance and indicates that carrageenan impairs glucose tolerance, increases insulin resistance and inhibits insulin signalling in vivo in mouse liver and human HepG2 cells. These effects may result from carrageenan-induced inflammation. The results demonstrate extra-colonic manifestations of ingested carrageenan and suggest that carrageenan in the human diet may contribute to the development of diabetes.