Fayyaz Susann, Japtok Lukasz, Kleuser Burkhard
Faculty of Mathematics and Natural Science, Institute of Nutritional Science, Department of Toxicology, University of Potsdam, Potsdam, Germany.
Cell Physiol Biochem. 2014;34(1):134-47. doi: 10.1159/000362990. Epub 2014 Jun 16.
Insulin resistance is a complex metabolic disorder in which insulin-sensitive tissues fail to respond to the physiological action of insulin. There is a strong correlation of insulin resistance and the development of type 2 diabetes both reaching epidemic proportions. Dysfunctional lipid metabolism is a hallmark of insulin resistance and a risk factor for several cardiovascular and metabolic disorders. Numerous studies in humans and rodents have shown that insulin resistance is associated with elevations of non-esterified fatty acids (NEFA) in the plasma. Moreover, bioactive lipid intermediates such as diacylglycerol (DAG) and ceramides appear to accumulate in response to NEFA, which may interact with insulin signaling. However, recent work has also indicated that sphingosine 1-phosphate (S1P), a breakdown product of ceramide, modulate insulin signaling in different cell types. In this review, we summarize the current state of knowledge about S1P and insulin signaling in insulin sensitive cells. A specific focus is put on the action of S1P on hepatocytes, pancreatic β-cells and skeletal muscle cells. In particular, modulation of S1P-signaling can be considered as a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes.
胰岛素抵抗是一种复杂的代谢紊乱，其中胰岛素敏感组织无法对胰岛素的生理作用产生反应。胰岛素抵抗与2型糖尿病的发生密切相关，二者均呈流行趋势。脂质代谢功能障碍是胰岛素抵抗的一个标志，也是多种心血管和代谢紊乱的危险因素。在人类和啮齿动物中进行的大量研究表明，胰岛素抵抗与血浆中非酯化脂肪酸（NEFA）水平升高有关。此外，生物活性脂质中间体如二酰甘油（DAG）和神经酰胺似乎会因NEFA而积累，它们可能与胰岛素信号传导相互作用。然而，最近的研究也表明，神经酰胺的分解产物鞘氨醇-1-磷酸（S1P）在不同细胞类型中调节胰岛素信号传导。在本综述中，我们总结了目前关于S1P和胰岛素敏感细胞中胰岛素信号传导的知识状态。特别关注S1P对肝细胞、胰腺β细胞和骨骼肌细胞的作用。特别是，调节S1P信号传导可被视为治疗胰岛素抵抗和2型糖尿病的潜在治疗靶点。
