摘要
在横纹肌和脂肪组织中,胰岛素可促进葡萄糖转运蛋白-4(GLUT-4)从细胞质内的GLUT-4储存囊泡(GSV)向细胞膜上移位。这一过程包括了GSV与细胞膜的融合及其调节机制。融合过程需要囊泡相关性膜蛋白2以及突触融合蛋白4和突触小体相关蛋白23的参与。Munc18c、synip以及b-Tomosyn起调节作用。胰岛素信号转导途径中的蛋白激酶B和蛋白激酶Cζ可能通过对Munc18c和synip的作用促进GLUT-4的移位。蛋白激酶B可能通过对synip的磷酸化来促进膜融合的过程,也可能通过抑制其底物AS160所具有的激活GTP酶的活性,来开放某一种或几种Rab蛋白,而开放的Rab蛋白则可以作用于Munc18c,促进膜融合过程。蛋白激酶Cζ则通过80K-H与Munc18c形成复合物,调节Munc18c对膜融合的作用。对胰岛素作用下GSV与细胞膜融合过程的研究,有助于认识胰岛素抵抗的产生机制。
Insulin stimulates the translocation of glucose transporter 4 （GLUT-4） from intracellular GLUT- 4 storage vesicles （GSV） to cell membrane in striated muscles and adipose tissue. This involves the membrane fusion process occurred between GSV and cell membrane as well as its regulatory mechanism. VAMFE expressed on GSV as the v-SNARE, as well as syntaxin 4 and SNAP23 on cell membrane as the t-SNAREs, are necessary for the membrane fusion. Munc18c, synip, and b-Tomosyn are involved in the regulation of the fusion process by modulating the SNAREs. Protein kinase（PK）B and PKCζ in the insulin signaling pathway are also important for the process, because of their potential roles in the interactions with Munc18c and synip. PKB may promote the fusion process by phosphorylafing synip, and（or） by inhibiting the GTPase-activating feature of AS160. As a result, one or more of the Rab proteins that interact with Munc18c and subsequently re, date the membrane fusion are opened. At the same time, a PKCζ/80K-H/Munc18c compound is formed to reinforce the Munc18c activity. It is essential for us to discover new mechanisms contributing to the development of insulin resistance from the study of GLUT-4 membrane fusion.
出处
《国际内分泌代谢杂志》
2006年第6期378-381,共4页
International Journal of Endocrinology and Metabolism
