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微小 RNA 在糖尿病并发症发展中的作用。

microRNA in the development of diabetic complications.

机构信息

*JDRF Danielle Alberti Memorial Centre for Diabetes Complications, Diabetes Division, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Victoria 3004, Australia.

出版信息

Clin Sci (Lond). 2014 Jan;126(2):95-110. doi: 10.1042/CS20130079.

Abstract

Today's world population is currently faced with a new type of non-transmissible pandemic: obesity. This lifestyle-related condition is driving the emergence of the diabetes pandemic through the development of low-level chronic inflammation. In recent years, a novel class of non-coding RNA, microRNA (miRNA), have emerged as being important regulators of numerous biological functions. Among these functions are basic maintenance of cell signalling and tissue architecture. Disruption of miRNA levels can contribute not only to the development of the chronic inflammation observed in obese diabetics, but also the development of both pancreatic β-cell dysfunction and loss, along with insulin resistance in metabolic tissues. These primary events set the scene for dysfunction of other tissues, including the retina, kidney, peripheral nerves, heart and the vasculature as a whole. Here, miRNAs again play a deterministic role in the development of a range of diseases collectively termed diabetic complications. Disturbances in miRNA levels appear to be reflected in the serum of patients and this may prove to be diagnostic in patients prior to clinical manifestation of disease, thus improving management of diabetes and its associated complications. Not only are miRNAs displaying promise as an early biomarker for disease, but a number of these miRNAs are displaying therapeutic potential with several in pre-clinical development. The present review aims to highlight our current understanding of miRNAs and their interaction with inflammatory signalling in the development and progression of diabetes and its complications. Utilization of miRNAs as biomarkers and therapeutic targets will also be considered.

摘要

当今世界人口正面临一种新型的非传染性大流行病

肥胖症。这种与生活方式相关的疾病通过引发低水平慢性炎症导致糖尿病大流行。近年来,一类新的非编码 RNA,即 microRNA(miRNA),已成为调节许多生物学功能的重要调控因子。这些功能包括细胞信号和组织架构的基本维持。miRNA 水平的紊乱不仅会导致肥胖型糖尿病患者中观察到的慢性炎症的发展,还会导致胰腺β细胞功能障碍和丧失以及代谢组织的胰岛素抵抗。这些最初的事件为其他组织(包括视网膜、肾脏、周围神经、心脏和整个血管系统)的功能障碍奠定了基础。在这里,miRNA 再次在一类被称为糖尿病并发症的多种疾病的发展中起决定性作用。miRNA 水平的紊乱似乎反映在患者的血清中,这在疾病临床表现之前可能具有诊断价值,从而改善糖尿病及其相关并发症的管理。miRNA 不仅显示出作为疾病早期生物标志物的潜力,而且其中一些 miRNA 具有治疗潜力,一些正在临床前开发中。本文综述旨在强调我们目前对 miRNA 及其在糖尿病及其并发症的发生和发展过程中与炎症信号相互作用的理解。还将考虑将 miRNAs 用作生物标志物和治疗靶标。

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