Hyperglycemia, Oxidative Stress, and Identification of Oxidative Stress Parameters in Type 2 Diabetes

Abstract

Oxidative stress is an important actor that can play a role in both the development of Type 2 diabetes and the development of diabetes complications. Basically, oxidative stress is used to describe the physiological state resulting from the disruption of the balance between the production and degradation of reactive oxygen derivatives (ROS). Data obtained from clinical studies show that systemic oxidative stress is closely related to metabolic syndrome and its components. Chronic hyperglycemia and hyperlipidemia are important risk factor for ROS formation. The contribution of hyperglycemia to ROS accumulation can occur through different metabolic pathways. Increased activity of the glycolytic pathway under hyperglycemic conditions and electron pressure on the mitochondrial electron transport system contribute to ROS formation. The formation and accumulation of reactive oxygen derivatives forces the cell to metabolize glucose with alternative pathways by suppressing the activity of glyceraldehyde 3-P dehydrogenase (GAPDH) enzyme which is one of the key enzymes involved in glycolysis. While the effectiveness of the glycolysis and krebs cycle decreases, polyol pathway, hexosamine pathway and Protein Kinase C (PCK) activity increase. All of these alternative metabolic pathways further increase ROS formation in the cell. ROS accumulation may contribute to the pathogenesis of insulin resistance by reducing the gene expression of insulin and the release of insulin from beta cells via posttranslational factors. ROS accumulation due to hyperglycemia also plays an important role in the development of diabetes complications. The results of clinical studies indicate that many markers can be used to determine the oxidative damage caused by diabetes and its complications in the protein, lipid and nucleic acid components of the cell and these markers may also give an idea about the level of oxidant damage

Keywords

• Hyperglycemia
• Reactive oxygen species
• Alternative metabolic pathways
• Type 2 diabetes

Hiperglisemi, Oksidatif Stres ve Tip 2 Diyabette Oksidatif Stres Belirteçlerinin Tanımlanması

Abstract

Oksidatif stres, hem Tip 2 diyabet oluşumu hem de diyabet komplikasyonlarının gelişiminde rol oynayabilen önemli bir aktördür. Temel olarak oksidatif stres, reaktif oksijen türevlerinin (ROS) yapımı ve bozunumu arasındaki dengenin bozulması sonucunda oluşan fizyolojik durumu tanımlamada kullanılır. Klinik çalışmalar sonucu elde edilen veriler, sistemik oksidatif stresin metabolik sendrom ve komponentleriyle yakından ilişkili olduğunu göstermektedir. Kronik hiperglisemi ve hiperlipidemi, ROS oluşumu için önemli risk faktörleridir. Hipergliseminin, ROS birikimine katkısı farklı metabolik yolaklar üzerinden gerçekleşebilmektedir. Temel olarak hiperglisemik koşullarda glikolitik yolağın aktivitesinin artması ve mitokondriyal elektron taşıma sistemi üzerinde oluşan elektron basıncı, ROS oluşumuna katkı sağlar. Reaktif oksijen türevlerinin oluşumu ve birikimi daha sonra glikolizde görevli kilit enzimlerden gliseraldehit 3-P dehidrogenaz (GAPDH) enzim aktivitesini baskılayarak hücreyi, glikozu alternatif yolaklarla metabolize etmeye zorlar. Glikoliz ve krebs döngüsünün etkinliği azalır; polyol yolağı, hekzozamin yolağı ve protein kinaz C (PCK) aktivitesi artar. Tüm bu alternatif metabolik yolaklar hücrede ROS oluşumunu daha da artırır. ROS birikimi, insülinin gen ekspresyonunu ve beta hücrelerden insülin salınımını posttranslasyonel faktörler aracılığıyla azaltarak, insülin direnci patogenezine katkı sağlayabilir. Hiperglisemi kaynaklı ROS birikimi, diyabet komplikasyonlarının oluşumunda da önemli role sahiptir. Klinik çalışmaların sonuçları, diyabet ve komplikasyonlarının, hücrenin protein, lipit ve nükleik asit komponentlerinde yarattığı oksidatif hasarı belirlemede pek çok belirtecin kullanılabileceğini ve bu belirteçlerin oksidan harabiyetin düzeyi hakkında fikir verebileceğini göstermektedir.

Keywords

• Hiperglisemi
• reaktif oksijen türevleri
• alternatif metabolik yolaklar
• Tip 2 diyabet

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