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2型糖尿病中白细胞转运失调:机制与潜在治疗途径

Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues.

作者信息

Pezhman Laleh, Tahrani Abd, Chimen Myriam

机构信息

Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom.

出版信息

Front Cell Dev Biol. 2021 Feb 22;9:624184. doi: 10.3389/fcell.2021.624184. eCollection 2021.

Abstract

Type 2 Diabetes Mellitus (T2DM) is a chronic inflammatory disorder that is characterized by chronic hyperglycemia and impaired insulin signaling which in addition to be caused by common metabolic dysregulations, have also been associated to changes in various immune cell number, function and activation phenotype. Obesity plays a central role in the development of T2DM. The inflammation originating from obese adipose tissue develops systemically and contributes to insulin resistance, beta cell dysfunction and hyperglycemia. Hyperglycemia can also contribute to chronic, low-grade inflammation resulting in compromised immune function. In this review, we explore how the trafficking of innate and adaptive immune cells under inflammatory condition is dysregulated in T2DM. We particularly highlight the obesity-related accumulation of leukocytes in the adipose tissue leading to insulin resistance and beta-cell dysfunction and resulting in hyperglycemia and consequent changes of adhesion and migratory behavior of leukocytes in different vascular beds. Thus, here we discuss how potential therapeutic targeting of leukocyte trafficking could be an efficient way to control inflammation as well as diabetes and its vascular complications.

摘要

2型糖尿病(T2DM)是一种慢性炎症性疾病,其特征为慢性高血糖和胰岛素信号传导受损,除了由常见的代谢失调引起外,还与各种免疫细胞数量、功能及活化表型的变化有关。肥胖在T2DM的发生发展中起核心作用。源自肥胖脂肪组织的炎症会全身性发展,并导致胰岛素抵抗、β细胞功能障碍和高血糖。高血糖也会导致慢性低度炎症,进而损害免疫功能。在本综述中,我们探讨了在炎症条件下,先天性和适应性免疫细胞的转运在T2DM中是如何失调的。我们特别强调了肥胖相关的白细胞在脂肪组织中的积聚,这会导致胰岛素抵抗和β细胞功能障碍,进而导致高血糖,并随之改变白细胞在不同血管床中的黏附和迁移行为。因此,我们在此讨论,针对白细胞转运进行潜在的治疗靶向为何可能是控制炎症以及糖尿病及其血管并发症的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae2b/7937619/3c968a30ee8f/fcell-09-624184-g001.jpg

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