Премьер мёртвое море маска с эффектом подтяжки с эластином и бета-каротином

Глютатион и диабет

Автор: VHandJMfan

Volume 1822, Issue 5, May 2012, Pages 729–736

Antioxidants and Antioxidant Treatment in Disease

Edited By D.A. Butterfield and J.N. Keller


Oxidative stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a cellular adaptive response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative stress and cellular stress response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic cellular stress response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P < 0.05 and P < 0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p < 0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

Graphical abstract

Full-size image (15 K)


► Oxidative stress plays a key role in diabetes mellitus and its complications. ► This study evaluates oxidative stress and stress response in diabetic patients. ► Sirtuin and Hsp signals counteract systemic oxidant status.


  • Type 2 diabetes;
  • Redox signaling;
  • Cellular stress response;
  • Glutathione status;
  • Sirtuins;
  • Vitagenes

1. Introduction

Oxidative stress is caused by an unbalance between a relative overload of oxidants and a depletion of antioxidants, and it is implicated in the pathogenesis of several chronic diseases, including atherosclerosis, ischaemia/reperfusion injury, chronic inflammatory diseases, renal failure and diabetes mellitus [1], [2], [3] and [4]. As a consequence of the increased burden of oxidative stress severe damage to DNA, proteins and lipids occur [1]. With regard to the role of oxidative stress in the pathogenesis and in the clinical history of diabetes mellitus, compelling evidences have been provided that both Type 1 and Type 2 diabetic patients are under conditions of an increased oxidative stress and that the complications of diabetes mellitus are partially mediated by oxidative stress [4], [5] and [6]. Several mechanisms seem to be involved in the genesis of oxidative stress in diabetic patients. Among these, glucose autoxidation, non enzymatic protein glycation as well as the formation of advanced-glycation end-products (AGEs) have been demonstrated in patients with diabetes and a direct relationship with the circulating blood glucose levels and glucose variability has been repeatedly demonstrated [5], [7] and [8]. In particular, it has been shown that two subclasses of AGEs, such as N-ε(carboxymethyl)lysine and pentosidine, accumulate in various tissues of poorly controlled diabetic patients [9]. The interplay between oxidative stress and AGEs is very complex. In fact, reactive oxygen species (ROS) accelerate the formation of AGEs, which in turn, as glycated proteins, are also able to produce ROS via complex biochemical mechanisms [10], [11] and [12]. During these reactions, protein modifications take place and compounds with a carbonyl or dicarbonyl moieties are formed [5].

In addition to the above mentioned AGEs and protein carbonyls, various other products derived from lipid peroxidation accumulate in biological fluids and tissues of diabetic patients. 4-hydroxy-2-nonenal (HNE) is considered an important marker of lipid peroxidation, but at the same time it is directly involved in both citotoxicity and mutagenic activity. In fact, 4-HNE further reacts with protein residues, such as histidine, to generate stable Michael adducts [13] and [14]. Interestingly, HNE-modified proteins have been identified in the serum and in renal tissues of type 2 diabetic patients [13] and [15]. The free radical-based oxidation of arachidonic acid [16] and [17] is one of the most relevant biochemical pathways that generate isoprostanes. Increased levels of F2-isoprostanes can be found in the plasma or urine of patients affected by several chronic inflammatory or degenerative diseases, including diabetes, and are currently used as in vivo indicators of lipid peroxidation [5], [18], [19], [20] and [21]. It is of interest that in addition to their well known role as in indicator of the oxidative stress status, several lines of evidences demonstrate that F2-isoprostanes are directly involved in vascular function and endothelial mediated platelet aggregation [22], [23] and [24].

Источник: http://www.sciencedirect.com/science/article/pii/S...

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