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抗氧化预处理的理由(或如何在氧化应激下保护胰岛素介导的作用)。

Justification for antioxidant preconditioning (or how to protect insulin-mediated actions under oxidative stress).

作者信息

Orzechowski A

机构信息

Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, 02-787 Warsaw, Nowoursynowska 159, Poland.

出版信息

J Biosci. 2003 Feb;28(1):39-49. doi: 10.1007/BF02970130.

Abstract

Insulin resistance is characterized by impaired glucose utilization in the peripheral tissues, accelerated muscle protein degradation, impaired antioxidant defences and extensive cell death. Apparently, both insulin and IGF-1 at physiological concentrations support cell survival by phosphatidylinositol 3 kinase-dependent and independent mechanisms. Postprandial hyperglycemia and hyperinsulinemia are found in insulin resistance, which accompanies the so-called noninsulin dependent diabetes mellitus (diabetes type 2). Evidence also indicates that increased susceptibility of muscle cells and cardiomycoytes to oxidative stress is among the harmful complications of insulin resistance and diabetes. Limited knowledge showing benefits of preconditioning with anti- oxidants (vitamin C, E, a-lipoic acid, N-acetylcysteine) in order to protect insulin action under oxidative stress prompted the author to discuss the theoretical background to this approach. It should be stressed that antioxidant preconditioning is relevant to prevention of both diabetes- and insulin resistance-associated side-effects such as low viability and cell deletion. Furthermore, antioxidant conditioning promises to provide higher efficacy for clinical applications in myoblast transfer therapy and cardiomyoplasty.

摘要

胰岛素抵抗的特征是外周组织葡萄糖利用受损、肌肉蛋白降解加速、抗氧化防御功能受损以及广泛的细胞死亡。显然,生理浓度的胰岛素和胰岛素样生长因子-1(IGF-1)通过磷脂酰肌醇3激酶依赖性和非依赖性机制支持细胞存活。胰岛素抵抗时会出现餐后高血糖和高胰岛素血症,这与所谓的非胰岛素依赖型糖尿病(2型糖尿病)相伴。有证据还表明,肌肉细胞和心肌细胞对氧化应激的易感性增加是胰岛素抵抗和糖尿病的有害并发症之一。关于在氧化应激下使用抗氧化剂(维生素C、E、α-硫辛酸、N-乙酰半胱氨酸)进行预处理以保护胰岛素作用的益处的知识有限,这促使作者讨论这种方法的理论背景。应该强调的是,抗氧化剂预处理与预防糖尿病和胰岛素抵抗相关的副作用(如低活力和细胞缺失)有关。此外,抗氧化预处理有望在成肌细胞移植治疗和心肌成形术中为临床应用提供更高的疗效。

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