İLERİ GLİKASYON ÜRÜNLERİNİN GÜÇLÜ BİR İNDÜKLEYİCİSİ OLAN METİLGLİOKSALIN DİYABET ÜZERİNE ETKİSİ

Öz

Metilglioksal (MGO), esas olarak glukoz ve fruktoz metabolizmasından türetilen reaktif bir bileşiktir. Bu metabolit güçlü bir ileri glikasyon ürünleri (AGE) öncüsü olması nedeniyle diyabetik komplikasyonlarda rol oynamaktadır. Diyabet dünya çapında en sık görülen hastalıklardan biri olup, DSÖ tarafından epidemik ilan edilmiştir. Diyabet; metabolik bozukluk, nöropati, retinopati, ateroskleroz ve diyabetik nefropati gibi majör komplikasyonlarla; bunların şiddeti/ciddiyeti ise hiperglisemi ile ilişkilidir. Metabolizmada gözlenen bu komplikasyonlar yüksek glukoz/fruktoz tüketimine bağlı olarak tetiklenerek dolaşımdaki AGE seviyelerini arttırır. Ayrıca, indirgen şekerler ve MGO gibi reaktif karbonil türleri, proteinlerin, lipitlerin ve DNA'nın glikasyonuna ve hatta hücrelerde ve dokularda AGE'lerin kademeli olarak birikmesine yol açar. AGE'lerin diyabet komplikasyonlarının patogenezinde yer aldığı ve MGO'nun insülin direncinde ve beta hücre fonksiyon bozukluğunda rol oynadığı son yıllarda yapılan klinik çalışmalarda rapor edilmiştir. Son yıllarda MGO'yu temizleyen ve AGE oluşumunu engelleyen birçok ilaç geliştirilmiş olmasına rağmen, MGO'nun neden olduğu mekanizmaları önleyecek etkili bir strateji bulunmamaktadır. En önemli AGE sınırlayıcı önlem beslenme alışkanlıklarındaki değişikliklere bağlıdır. Bu derlemenin amacı özellikle MGO’nun oluşumu, detoksifikasyonu ve etki mekanizmalarını özetlemekte ve diyabetin patofizyolojisi ve komplikasyonları üzerindeki etkisi hakkındaki bilgileri güncel çalışmalar ışığında değerlendirmektir.

Anahtar Kelimeler

• Metilglioksal
• ileri glikasyon ürünleri
• diyabet

EFFECT OF METHYLGLYOXAL, A POWERFUL INDUCER OF ADVANCED GLICATION PRODUCTS, ON DIABETES

Öz

Methylglyoxal (MGO) is a reactive compound derived mainly from glucose and fructose metabolism. This metabolite has been implicated in diabetic complications as it is a potent advanced glycation products (AGE) precursor. Diabetes is one of the most common diseases worldwide and has been declared epidemic by the WHO. Diabetes is associated with major complications such as metabolic disorders, neuropathy, retinopathy, atherosclerosis and diabetic nephropathy, the severity of which is associated with hyperglycemia. These metabolic complications are triggered by high glucose/fructose consumption, which increases circulating levels of AGEs. Furthermore, reducing sugars and reactive carbonyl species such as MGO lead to glycation of proteins, lipids and DNA, and even to the gradual accumulation of AGEs in cells and tissues. Recent clinical studies have reported that AGEs are involved in the pathogenesis of diabetes complications and that MGO plays a role in insulin resistance and beta cell dysfunction. Although many drugs that clear MGO and prevent the formation of AGEs have been developed in recent years, there is no effective strategy to prevent the mechanisms caused by MGO. The most important AGEs limiting measure depends on changes in dietary habits. The aim of this review is to summarize the formation, detoxification and mechanisms of action of MGO and to provide information on its impact on the pathophysiology and complications of diabetes.

Anahtar Kelimeler

• Methylglyoxal
• advanced glycation products
• diabetes

Kaynakça

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