Circulating sphingolipid biomarkers in models of type 1 diabetes
Circulating sphingolipid biomarkers in models of type 1 diabetes
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DOI：
10.1194/jlr.m010595
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发表时间：
2011-03-01
影响因子：
6.5
通讯作者：
Kester, Mark
中科院分区：
文献类型：
--
作者：
Fox, Todd E.;Bewley, Maria C.;Kester, Mark
脂质代谢的改变可能导致糖尿病并发症。鞘脂是细胞膜的重要组成部分，在体内平衡以及疾病的发生和发展中起着关键作用。然而，鞘脂在1型糖尿病中的作用在很大程度上仍未被探索。因此，我们试图通过液相色谱 - 串联质谱（LC - MS/MS）对两种1型糖尿病动物模型（链脲佐菌素诱导的糖尿病大鼠和Ins2（Akita）糖尿病小鼠）中的鞘脂代谢物进行定量，以确定潜在的治疗靶点和生物标志物。结果显示，与相应的对照动物相比，两种糖尿病模型中的1 - 磷酸鞘氨醇（S1P）均升高。此外，糖尿病动物的血浆中含ω - 9 24:1（神经酸）的神经酰胺、鞘磷脂和脑苷脂水平降低。在肝脏和心脏中也观察到24:1酯化鞘脂的减少。高脂肪饮食导致的营养应激也降低了小鼠血浆和肝脏中的24:1含量，在同时患有糖尿病的某些情况下，这种降低更为严重。皮下注射胰岛素纠正了小鼠糖尿病模型中循环的S1P和24:1水平。因此，循环鞘脂的变化，如生物活性S1P的增加以及对心脏和神经有保护作用的ω - 9酯化鞘脂的减少，可作为1型糖尿病的生物标志物，并代表新的治疗靶点。——福克斯（Fox），T. E.；贝利（Bewley），M. C.；昂拉斯（Unrath），K. A.；佩德森（Pedersen），M. M.；安德森（Anderson），R. E.；荣（Jung），D. Y.；杰斐逊（Jefferson），L. S.；金（Kim），J. K.；布朗森（Bronson），S. K.；弗拉纳根（Flanagan），J. M.；凯斯特（Kester），M.《1型糖尿病模型中循环鞘脂生物标志物》，《脂质研究杂志》2011年，52卷：509 - 517页。
Alterations in lipid metabolism may contribute to diabetic complications. Sphingolipids are essential components of cell membranes and have essential roles in homeostasis and in the initiation and progression of disease. However, the role of sphingolipids in type 1 diabetes remains largely unexplored. Therefore, we sought to quantify sphingolipid metabolites by LC-MS/MS from two animal models of type 1 diabetes (streptozotocin-induced diabetic rats and Ins2(Akita) diabetic mice) to identify putative therapeutic targets and biomarkers. The results reveal that sphingosine-1-phosphate (So1P) is elevated in both diabetic models in comparison to respective control animals. In addition, diabetic animals demonstrated reductions in plasma levels of omega-9 24:1 (nervonic acid)-containing ceramide, sphingomyelin, and cerebrosides. Reduction of 24:1-esterfied sphingolipids was also observed in liver and heart. Nutritional stress via a high-fat diet also reduced 24:1 content in the plasma and liver of mice, exacerbating the decrease in some cases where diabetes was also present. Subcutaneous insulin corrected both circulating So1P and 24:1 levels in the murine diabetic model.jlr Thus, changes in circulating sphingolipids, as evidenced by an increase in bioactive So1P and a reduction in cardio-and neuro-protective omega-9 esterified sphingolipids, may serve as biomarkers for type 1 diabetes and represent novel therapeutic targets.-Fox, T. E., M. C. Bewley, K. A. Unrath, M. M. Pedersen, R. E. Anderson, D. Y. Jung, L. S. Jefferson, J. K. Kim, S. K. Bronson, J. M. Flanagan, and M. Kester. Circulating sphingolipid biomarkers in models of type 1 diabetes. J. Lipid Res. 2011. 52: 509-517.