Production and Internalization of Extracellular Vesicles in Norm and under Conditions of Hyperglycemia and Insulin Resistance

IF 0.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Pub Date : 2022-05-17 DOI:10.1134/S199075082202010X

N. V. Yunusova, E. E. Dandarova, D. A. Svarovsky, N. S. Denisov, D. N. Kostromitsky, M. R. Patysheva, O. V. Cheremisina, L. V. Spirina

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引用次数: 1

Abstract—

Extracellular vesicles (EVs) are spherical functionally important structures of cell membrane origin ranging in size from 40 nm to 5000 nm. They are involved in the horizontal transfer of mainly proteins and microRNAs. The mechanisms of EV internalization include clathrin-dependent endocytosis, caveolin-dependent endocytosis, raft-mediated endocytosis, and macropinocytosis. Type 2 diabetes mellitus (T2DM) is a common group of metabolic disorders in adults; the incidence and prevalence of T2DM increase in parallel with the obesity epidemic. Since adipose tissue plays a key role in the development of insulin resistance, EVs secreted by adipose tissue may be considered as an information transmitter in this process. EVs of the adipocyte origin are predominantly captured up by tissue macrophages, adipocytes themselves, hepatocytes, and skeletal muscles. The EV uptake promotes M1 polarization of macrophages, a decrease in glucose uptake by hepatocytes and myocytes due to the transfer of functionally active microRNAs influencing carbohydrate and lipid metabolism. Patients with T2DM and impaired glucose tolerance, have a significantly higher level of CD235a-positive (erythrocyte) EVs and a trend to the increase in CD68-positive (leukocyte) and CD62p-positive (platelet/endothelial cells) EVs. The levels of CD31+/CD146-positive EVs (endothelial cells) were comparable between diabetic and euglycemic patients. EVs from diabetic patients were preferentially internalized by monocytes (predominantly classical and transitional, and to a lesser extent nonclassical monocyte fractions) and B cells as compared to euglycemic patients. Internalization of EVs from patients with T2DM by monocytes led to a decrease in their apoptosis, changes in differentiation, and suppression of monocyte reactions controlling oxidative stress. Thus, insulin resistance increases the secretion of EVs, which are preferentially internalized by monocytes and alter their function. EVs are considered as sources of promising clinical markers of insulin resistance, complications of diabetes mellitus (endothelial dysfunction, retinopathy, nephropathy, neuropathy), and EV markers can also be used to monitor the effectiveness of therapy for these complications.

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正常及高血糖和胰岛素抵抗条件下细胞外囊泡的产生和内化

摘要/ abstract摘要:细胞外囊泡(EVs)是起源于细胞膜的具有重要功能的球形结构，大小在40 ~ 5000nm之间。它们主要参与蛋白质和microrna的水平转移。EV内化的机制包括网格蛋白依赖的内吞作用、小窝蛋白依赖的内吞作用、筏子介导的内吞作用和巨噬细胞作用。2型糖尿病(T2DM)是一种常见的成人代谢性疾病;2型糖尿病的发病率和流行率与肥胖流行同步增加。由于脂肪组织在胰岛素抵抗的发展中起着关键作用，脂肪组织分泌的EVs可能被认为是这一过程中的信息传递者。脂肪细胞来源的EVs主要被组织巨噬细胞、脂肪细胞本身、肝细胞和骨骼肌捕获。EV摄取促进巨噬细胞的M1极化，肝细胞和肌细胞由于影响碳水化合物和脂质代谢的功能活性microrna的转移而减少葡萄糖摄取。伴有糖耐量受损的T2DM患者，cd235a阳性(红细胞)EVs水平明显升高，cd68阳性(白细胞)和cd62p阳性(血小板/内皮细胞)EVs有升高的趋势。CD31+/ cd146阳性EVs(内皮细胞)水平在糖尿病患者和正常血糖患者之间具有可比性。与血糖正常的患者相比，糖尿病患者的ev更倾向于被单核细胞(主要是经典和过渡性单核细胞，以及较小程度的非经典单核细胞)和B细胞内化。T2DM患者EVs被单核细胞内化导致其凋亡减少，分化改变，单核细胞控制氧化应激的反应受到抑制。因此，胰岛素抵抗增加了ev的分泌，这些ev被单核细胞优先内化并改变了它们的功能。EVs被认为是胰岛素抵抗、糖尿病并发症(内皮功能障碍、视网膜病变、肾病、神经病变)的有希望的临床标志物的来源，EVs标志物也可用于监测治疗这些并发症的有效性。

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来源期刊

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

1.10

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0.00%

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期刊介绍： Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry covers all major aspects of biomedical chemistry and related areas, including proteomics and molecular biology of (patho)physiological processes, biochemistry, neurochemistry, immunochemistry and clinical chemistry, bioinformatics, gene therapy, drug design and delivery, biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine. The journal also publishes review articles. All issues of the journal usually contain solicited reviews.