The role of sphingolipid signalling in diabetes‑associated pathologies (Review).
The role of sphingolipid signalling in diabetes‑associated pathologies (Review).
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DOI：
10.3892/ijmm.2017.2855
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发表时间：
2017-02
影响因子：
5.4
通讯作者：
Sukocheva OA
中科院分区：
文献类型：
--
作者：
Ng ML;Wadham C;Sukocheva OA
鞘氨醇激酶(SphK)是一种重要的信号转导酶，催化鞘氨醇(Sph)磷酸化形成1-磷酸鞘氨醇(S1P)。多功能脂质S1P与五个G蛋白偶联受体(GPCRs)家族结合。作为细胞内的第二信使，S1P激活了负责维持鞘磷脂代谢的关键信号级联反应，并参与了癌症的进展以及其他炎症性和代谢性疾病的发展。SphK和S1P是调节细胞增殖、存活、凋亡、黏附和迁移等多种代谢过程的关键分子。有强有力的证据支持SphK和S1P在糖尿病进展中的关键作用，包括胰岛素敏感性和胰岛素分泌、胰腺β细胞凋亡和糖尿病炎症状态的发展。本文就SphK/S1P信号转导作用与胰岛素抵抗、胰腺β细胞死亡和糖尿病血管并发症的研究现状作一综述。
Sphingosine kinase (SphK) is an important signalling enzyme that catalyses the phosphorylation of sphingosine (Sph) to form sphingosine-1-phosphate (S1P). The multifunctional lipid, S1P binds to a family of five G protein-coupled receptors (GPCRs). As an intracellular second messenger, S1P activates key signalling cascades responsible for the maintenance of sphingolipid metabolism, and has been implicated in the progression of cancer, and the development of other inflammatory and metabolic diseases. SphK and S1P are critical molecules involved in the regulation of various cellular metabolic processes, such as cell proliferation, survival, apoptosis, adhesion and migration. There is strong evidence supporting the critical roles of SphK and S1P in the progression of diabetes mellitus, including insulin sensitivity and insulin secretion, pancreatic β-cell apoptosis, and the development of diabetic inflammatory state. In this review, we summarise the current state of knowledge for SphK/S1P signalling effects, associated with the development of insulin resistance, pancreatic β-cell death and the vascular complications of diabetes mellitus.