The assembly of lipid droplets and its relation to cellular insulin sensitivity
The assembly of lipid droplets and its relation to cellular insulin sensitivity
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DOI：
10.1042/bst0370981
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发表时间：
2009-10-01
影响因子：
3.9
通讯作者：
Olofsson, Sven-Olof
中科院分区：
文献类型：
--
作者：
Bostrom, Pontus;Andersson, Linda;Olofsson, Sven-Olof
脂滴的组装依赖于激活PLD 1（磷脂酶D-1）的PtdIns（4，S）P-2，这对于组装过程是重要的。ERK 2（细胞外信号调节激酶2）磷酸化动力蛋白并将其分类为脂滴，使其在微管上转运。脂滴通过融合而变大，这依赖于动力蛋白和微管上的转移，并且由SNARE（可溶性N-乙基马来酰亚胺敏感融合蛋白-附着蛋白受体）蛋白SNAP-23（23 kDa突触体相关蛋白）、突触融合蛋白-5和VAMP-4（囊泡相关蛋白4）催化。SNAP-23还参与葡萄糖转运蛋白GLUT 4向质膜的胰岛素依赖性易位。脂肪酸诱导SNAP-23从质膜到细胞内部的错误分选，导致细胞胰岛素抵抗，这可以通过增加SNAP-23的水平来克服。在T2 D（2型糖尿病）患者的肌肉活检中，SNAP-23也发生了同样的体内错误分类。此外，在来自人尿道肌肉活检组织的质膜中SNAP-23的量与全身胰岛素敏感性之间存在线性关系。突触融合蛋白-5在T2 D患者中是低的，这导致At（也称为蛋白激酶B）的胰岛素依赖性磷酸化的减少。因此，SNAP-23和突触融合蛋白-5高度参与胰岛素抵抗的发展。
The assembly of lipid droplets is dependent on PtdIns(4,S)P-2 that activates PLD1 (phospholipase D-1), which is important for the assembly process. ERK2 (extracellular-signal-regulated kinase 2) phosphorylates the motor protein dynein and sorts it to lipid droplets, allowing them to be transported on microtubules. Lipid droplets grow in size by fusion, which is dependent on dynein and the transfer on microtubules, and is catalysed by the SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins SNAP-23 (23 kDa synaptosome-associated protein), syntaxin-5 and VAMP-4 (vesicle-associated protein 4). SNAP-23 is also involved in the insulin-dependent translocation of the glucose transporter GLUT4 to the plasma membrane. Fatty acids induce a missorting of SNAP-23, from the plasma membrane to the interior of the cell, resulting in cellular insulin resistance that can be overcome by increasing the levels of SNAP-23. The same missorting of SNAP-23 occurs in vivo in skeletal-muscle biopsies from patients with T2D (Type 2 diabetes). Moreover, there was a linear relation between the amount of SNAP-23 in the plasma membrane from human skeletal-muscles biopsies and the systemic insulin-sensitivity. Syntaxin-5 is low in T2D patients, which leads to a decrease in the insulin-dependent phosphorylation of At (also known as protein kinase B). Thus both SNAP-23 and syntaxin-5 are highly involved in the development of insulin resistance.