Targeting glucose metabolism for treatment of COVID-19.
Targeting glucose metabolism for treatment of COVID-19.
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DOI：
10.1038/s41392-021-00532-4
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发表时间：
2021-03-06
影响因子：
39.3
通讯作者：
Azizi Z
中科院分区：
文献类型：
--
作者：
Ardestani A;Azizi Z
Codo et al. 1在Cell Metabolism上发表的一项最新研究表明，在高糖条件下培养的SARS-CoV-2感染引起的人单核细胞的代谢重新连接高度诱导病毒复制和细胞因子产生，损害T细胞应答和功能。最终，这会引发肺上皮细胞死亡，并从机制上解释了为什么糖尿病患者可能更容易患上严重的COVID-19。由SARS-CoV-2引起的COVID-19是一个重大的公共卫生负担;其在全球范围内的高流行率对社会各个层面产生了巨大的影响。肥胖和相关代谢疾病，特别是2型糖尿病（T2 D）与更具破坏性的COVID-19疾病病程有关。2最近的流行病学数据表明，COVID-19导致的发病率以及死亡率在肥胖和T2 D人群中明显较高。2一致的是，多项临床研究，包括对大量COVID-19患者的回顾性检查，表明血糖水平控制不佳与最高的COVID-19死亡率相关。2这表明COVID-19的发病机制和宿主的代谢调节密切相关。目前对糖代谢失调的分子机制知之甚少，尤其是在胰岛素治疗下，这决定了糖尿病环境中细胞和器官对严重SARS-CoV-2疾病结果的脆弱性。病毒改变宿主细胞的代谢，以便为其快速有效的复制和传播创造最佳条件。一个关键的具体例子是增强对重要营养物质如葡萄糖的吸收，以支持代谢信号传导，即有氧糖酵解，葡萄糖代谢的主要途径及其用于生物合成反应的副产物。主要由胰岛素分泌和/或作用受损引起的异常葡萄糖代谢是T2 D的特征性特征，并影响对全身代谢调节非常重要的几种组织，如肝脏、脂肪细胞、肌肉、胰岛和免疫细胞。持续高血糖导致的葡萄糖代谢增加可能会增强SARS-CoV-2的进入和随后的复制，以及糖尿病患者的免疫反应加剧。因此，糖尿病中葡萄糖代谢紊乱和代谢紊乱可能是有利于SARS-CoV-2发病机制的内在细胞策略。在此背景下，Codo等人1探索了糖尿病条件下SARS-CoV-2感染的人单核细胞的分子反应。作者最初表明，SARS-CoV-2有效感染外周血单核细胞，上调血管紧张素转换酶2（ACE 2），这是SARS-CoV-2的关键受体，并高度诱导促炎细胞因子，如TNF-α，IL-1β和IL-6。这与先天免疫反应改变和炎症细胞因子过度产生，即所谓的“细胞因子风暴”相一致
A recent study published in Cell Metabolism by Codo et al. 1 shows that metabolic rewiring of human monocytes by SARS-CoV-2 infection cultured under high glucose highly induces viral replication and cytokine production compromising T-cell response and function. Ultimately, this triggers lung epithelial cell death and, mechanistically, provides an explanation why people with diabetes might be more susceptible to develop severe COVID-19. COVID-19 caused by the SARS-CoV-2 represents a significant public health burden; its high prevalence worldwide has dramatic consequences on the society at all levels. Obesity and related metabolic diseases particularly type 2 diabetes (T2D) are linked with more devastating COVID-19 disease courses. 2 Recent epidemiological data demonstrate that rate of COVID-19 induced morbidity as well as mortality is markedly higher in people with obesity and T2D. 2 Consistently, multiple clinical studies including a retrospective examination of a large cohort of COVID-19 patients have shown that poorly controlled blood glucose levels are associated with highest COVID-19 mortality rates. 2 This suggests that COVID-19 pathogenesis and the regulation of metabolism in the host are intimately connected. Little is known about the molecular mechanisms of deregulated glucose metabolism, especially under insulin therapy, that determine vulnerability of cells and organs in a diabetic environment to a severe SARS-CoV-2 disease outcome.Viruses alter the host cell metabolism in order to make optimal conditions for their rapid and efficient replication and spread. One key particular example is the enhanced uptake of important nutrients such as glucose to support metabolic signaling, ie, aerobic glycolysis, a primary pathway of glucose metabolism and its by-products for biosynthetic reactions. Abnormal glucose metabolism primarily caused by impaired insulin secretion and/or action is a characteristic feature of T2D and affects several tissues highly important for the regulation of whole body metabolism, such as liver, adipocytes, muscle, pancreatic islets, and immune cells. The increased glucose metabolism imposed by sustained hyperglycemia may enhance SARS-CoV-2’s entry and subsequent replication, as well as an exacerbated immune response in individuals with diabetes. Thus, a disrupted glucose metabolism and metabolic derangement in diabetes may be an intrinsic cellular strategy that favors SARS-CoV-2 pathogenesis. In this context, Codo et al. 1 explored the molecular response of SARS-CoV-2 infected human monocytes under diabetic condition. The authors initially show that SARS-CoV-2 efficiently infects peripheral blood monocytes, upregulates angiotensin-converting enzyme 2 (ACE2), a key SARS-CoV-2’s receptor and highly induced proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. This is consistent with the altered innate immune response and excessive inflammatory cytokine production, the so-called “cytokine storm”
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影响因子：
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