Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes.
Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes.
复制标题
DOI：
10.1007/s00018-011-0690-x
复制
发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Luiken JJ
中科院分区：
文献类型：
--
作者：
Steinbusch LK;Schwenk RW;Ouwens DM;Diamant M;Glatz JF;Luiken JJ
心肌细胞利用葡萄糖和脂肪酸生产ATP。这些底物通过葡萄糖转运蛋白4 （GLUT4）和脂肪酸转运蛋白CD36转运到细胞中。除了位于肌膜外，GLUT4和CD36还储存在细胞内的隔室中。升高的血浆胰岛素浓度和增加的心脏工作将刺激GLUT4和CD36转移到肌膜。据目前研究，调节GLUT4易位的信号通路类似地影响CD36易位。在胰岛素抵抗和2型糖尿病的发展过程中，CD36永久定位于肌膜，而GLUT4则内化。GLUT4和CD36的并置定位对于糖尿病心脏中异常的底物摄取是重要的：以葡萄糖为代价长期增加脂肪酸摄取。为了解释GLUT4和CD36在2型糖尿病中亚细胞定位的差异，最近的研究集中在参与亚细胞间货物运输的蛋白质的作用上。这些蛋白中的一些似乎与GLUT4和CD36易位相似。然而，其他基因在GLUT4或CD36易位中有不同的作用。这些转运成分不同地参与GLUT4或CD36易位，可能被认为是开发治疗方法的新靶点，以恢复肥胖、胰岛素抵抗和糖尿病性心肌病中不平衡的底物利用。
Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy.
登录
查看更多内容
DOI：
10.1152/ajpendo.00238.2002
发表时间：
2003-10-01
影响因子：
5.1
作者：
Ai, H;Ralston, E;Ploug, T
通讯作者：
Ploug, T
影响因子：
2
作者：
Choi, Young Ok;Park, Jong-Ha;Jang, Yeon Jin
通讯作者：
Jang, Yeon Jin
影响因子：
4.9
作者：
Bonen, A.;Tandon, N. N.;Heigenhauser, G. J. F.
通讯作者：
Heigenhauser, G. J. F.
影响因子：
20.1
作者：
Chiu, HC;Kovacs, A;Schaffer, JE
通讯作者：
Schaffer, JE
影响因子：
3
作者：
Carley, A. N.;Atkinson, L. L.;Severson, D. L.
通讯作者：
Severson, D. L.