鞘脂类对胰岛素信号的调控——Ⅱ型糖尿病研究的新兴领域

Modulation of Sphingolipids on Insulin Signal——an Emerging Research Field of Type 2 Diabetes Mellitus

胰岛素抵抗是Ⅱ型糖尿病的病理基础之一,近年来已成为Ⅱ型糖尿病研究的关键和热点.众多研究发现,机体内鞘脂类物质水平的改变直接影响胰岛素信号的强弱.神经酰胺和神经节苷脂GM3对胰岛素信号具有负向调控作用,介导胰岛素抵抗的形成,该调节效应依赖于细胞膜上微囊蛋白.1-磷酸鞘氨醇则通过氧化还原途径增强胰岛素信号.微囊蛋白功能性活动和1-磷酸鞘氨醇的介导作用均与钙信号相关,因此,可通过实时检测细胞外钙内流和细胞内钙瞬间变化,从离子通道水平进一步探索鞘脂类调节胰岛素信号的相关机制.本文综述了鞘脂类物质调控胰岛素信号的机制,干预鞘脂类水平和改善胰岛素抵抗的策略,将为鞘脂类物质在Ⅱ型糖尿病预防和治疗的研究及应用提供有力的帮助.

Insulin resistance is a pathological basis for the development of type 2 diabetes mellitus （T2DM）, and has been a key and hot topic for T2DM research recently. Furthermore, an increasing number of reports demonstrate that some sphingolipids play a critical role in regulating insulin signal. For instance, both ceramide and ganglioside monosialo 3 （GM3） can reduce insulin signal sensitivity and lead to insulin resistance. Their mechanisms may be associated with caveolin localization and formation of caveolae on membrane. On the contrary, another remarkable sphingolidid, sphingosine-1-phosphate （S 1P）, dramatically enhances insulin signal by redox signaling pathway. Both negative and positive effects of sphingolipids on insulin signal imply the involvement of calcium signal. Thus it can be seen that detecting both extracellular calcium influx and intracellular calcium transient in real time may satisfy the speculation of insulin signal regulation with sphingolipids at the ion channel level. Therefore, we will review the mechanisms of modulation of some sphingolipids, including ceramide, GM3 and S 1P, on insulin signal. The potential strategies of sphingolipids activity alteration and insulin resistance improvement will be involved in this review as well, which will make great strides in T2DM research.