Fischell Department of Bioengineering, University of Maryland, College Park, MD, U.S.A.
Biochem Soc Trans. 2021 Feb 26;49(1):313-325. doi: 10.1042/BST20200611.
The endothelial cell response to glucose plays an important role in both health and disease. Endothelial glucose-induced dysfunction was first studied in diabetic animal models and in cells cultured in hyperglycemia. Four classical dysfunction pathways were identified, which were later shown to result from the common mechanism of mitochondrial superoxide overproduction. More recently, non-coding RNA, extracellular vesicles, and sodium-glucose cotransporter-2 inhibitors were shown to affect glucose-induced endothelial dysfunction. Endothelial cells also metabolize glucose for their own energetic needs. Research over the past decade highlighted how manipulation of endothelial glycolysis can be used to control angiogenesis and microvascular permeability in diseases such as cancer. Finally, endothelial cells transport glucose to the cells of the blood vessel wall and to the parenchymal tissue. Increasing evidence from the blood-brain barrier and peripheral vasculature suggests that endothelial cells regulate glucose transport through glucose transporters that move glucose from the apical to the basolateral side of the cell. Future studies of endothelial glucose response should begin to integrate dysfunction, metabolism and transport into experimental and computational approaches that also consider endothelial heterogeneity, metabolic diversity, and parenchymal tissue interactions.
内皮细胞对葡萄糖的反应在健康和疾病中都起着重要作用。内皮细胞葡萄糖诱导的功能障碍首先在糖尿病动物模型和高血糖培养的细胞中进行了研究。确定了四个经典的功能障碍途径，后来证明这些途径是由于线粒体超氧化物过度产生的共同机制所致。最近，非编码 RNA、细胞外囊泡和钠-葡萄糖协同转运蛋白 2 抑制剂被证明会影响葡萄糖诱导的内皮功能障碍。内皮细胞也为自身的能量需求代谢葡萄糖。过去十年的研究强调了如何操纵内皮细胞的糖酵解来控制癌症等疾病中的血管生成和微血管通透性。最后，内皮细胞将葡萄糖转运到血管壁细胞和实质组织中。来自血脑屏障和外周血管的越来越多的证据表明，内皮细胞通过将葡萄糖从细胞的顶侧向基底外侧移动的葡萄糖转运蛋白来调节葡萄糖的转运。未来对内皮细胞葡萄糖反应的研究应开始将功能障碍、代谢和运输整合到实验和计算方法中，这些方法还应考虑内皮细胞的异质性、代谢多样性和实质组织相互作用。
