CD36 and GLUT4 are the main cardiac trans-sarcolemmal transporters for long-chain fatty acids and glucose, respectively. Together they secure the majority of cardiac energy demands. Moreover, these transporters each represent key governing kinetic steps in cardiac fatty acid and glucose fluxes, thereby offering major sites of regulation. The underlying mechanism of this regulation involves a perpetual vesicle-mediated trafficking (recycling) of both transporters between intracellular stores (endosomes) and the cell surface. In the healthy heart, CD36 and GLUT4 translocation to the cell surface is under short-term control of the same physiological stimuli, most notably increased contraction and insulin secretion. However, under chronic lipid overload, a condition that accompanies a Western lifestyle, CD36 and GLUT4 recycling are affected distinctly, with CD36 being expelled to the sarcolemma while GLUT4 is imprisoned within the endosomes. Moreover, the increased CD36 translocation towards the cell surface is a key early step, setting the heart on a route towards insulin resistance and subsequent contractile dysfunction. Therefore, the proteins making up the trafficking machinery of CD36 need to be identified with special focus to the differences with the protein composition of the GLUT4 trafficking machinery. These proteins that are uniquely dedicated to either CD36 or GLUT4 traffic may offer targets to rectify aberrant substrate uptake seen in the lipid-overloaded heart. Specifically, CD36-dedicated trafficking regulators should be inhibited, whereas such GLUT4-dedicated proteins would need to be activated. Recent advances in the identification of CD36-dedicated trafficking proteins have disclosed the involvement of vacuolar-type H+-ATPase and of specific vesicle-associated membrane proteins (VAMPs). In this review, we summarize these recent findings and sketch a roadmap of CD36 and GLUT4 trafficking compatible with experimental findings.

中文翻译：

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了解心肌胰岛素抵抗发展过程中CD36和GLUT4的不同亚细胞运输。

CD36和GLUT4分别是长链脂肪酸和葡萄糖的主要心脏反肌膜转运蛋白。它们共同确保了大多数心脏能量需求。此外，这些转运蛋白各自代表心脏脂肪酸和葡萄糖通量中关键的控制动力学步骤，从而提供了主要的调节位点。该调节的基本机制涉及在细胞内贮存体（内体）与细胞表面之间的两种转运蛋白的永久性囊泡介导的运输（再循环）。在健康的心脏中，CD36和GLUT4易位至细胞表面受相同生理刺激的短期控制，最明显的是收缩和胰岛素分泌增加。但是，在慢性脂质超负荷（伴随西方生活方式的状况）下，CD36和GLUT4的回收受到明显影响，CD36被驱逐到肌膜，而GLUT4被囚禁在内体中。此外，CD36向细胞表面转运的增加是关键的早期步骤，使心脏处于朝向胰岛素抵抗和随后的收缩功能障碍的道路上。因此，需要特别注意组成CD36转运蛋白的蛋白质，以区别于GLUT4转运蛋白的蛋白质组成。这些专门针对CD36或GLUT4流量的蛋白质可能提供目标，以纠正脂质超负荷心脏中异常的底物摄取。具体而言，应抑制CD36专用的运输调节剂，而此类GLUT4专用的蛋白则需要激活。CD36专用运输蛋白的鉴定的最新进展已公开了液泡型H + -ATPase和特定囊泡相关膜蛋白（VAMP）的参与。在这篇综述中，我们总结了这些最新发现，并概述了与实验结果兼容的CD36和GLUT4贩运路线图。