Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels. Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for health care systems. Therefore, and to counteract the continually increasing prevalence of diabetes, understanding the pathogenesis, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy. In this regard, research was performed revealing further evidence that oxidative stress has an important role in hyperglycemia-induced tissue injury as well as in early events relevant for the development of T2DM. The formation of advanced glycation end products (AGEs), a group of modified proteins and/or lipids with damaging potential, is one contributing factor. On the one hand it has been reported that AGEs increase reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions. Thus, AGEs contribute at least partly to chronic stress conditions in diabetes. As AGEs are not only formed endogenously, but also derive from exogenous sources, i.e., food, they have been assumed as risk factors for T2DM. However, the role of AGEs in the pathogenesis of T2DM and diabetic complications—if they are causal or simply an effect—is only partly understood. This review will highlight the involvement of AGEs in the development and progression of T2DM and their role in diabetic complications.

Influence of Varying Dietary Protein Levels on Glycation of Albumin, Tryptophan and Valine in the Plasma of Chickens

“…Since CML was first discovered as an AGE, various types of AGEs have been identified and reported, and detailed information about AGEs has been accumulated thus far (Nagai et al, 2014;Ashraf et al, 2015;Nowotny et al, 2015). Information about Amadori products, which are recognized as early glycation products, has also been accumulated similar to AGEs.…”

Aspectos oxidativos da síndrome metabólica e aterosclerose

“…No entanto, quando há uma quantidade maior de oxidantes em relação aos antioxidantes, o organismo fica vulnerável aos efeitos deletérios das espécies reativas e a inúmeros distúrbios metabólicos e fisiológicos. A essa condição dá-se o nome de estresse oxidativo [15][16][17][18][19][20].…”

“…É importante lembrar o efeito dos produtos avançados de glicação no aumento da formação de espécies reativas e nos processos inflamatórios relacionados ao DM2 e suas complicações. Após a instalação do DM2, o estresse oxidativo é responsável, pelo menos em parte, pela superprodução de espécies reativas de oxigênio, possivelmente em virtude da ação dos produtos avançados de glicação [20,23].…”

“…Também há ativação de NADPHoxidases, culminando na produção de espécies reativas de oxigênio, que por sua vez, aumentam a formação de produtos avançados de glicação. Neste contexto haverá ativação de fator nuclear-kappa B que ativa a transcrição de citocinas pró-inflamatórias, como a IL-6 e o peptídeo-1 quimiotático de monócitos, intensificando a resposta inflamatória [20,[24][25].…”

Study of Matrix Gla Protein G-7A and T-138C Gene Polymorphisms in Patients with Type 2 Diabetes Mellitus

“…Type 2 diabetes mellitus is a disease characterized by insulin resistance and cell failure leading to elevated blood glucose levels (1). Aortic calcifications and cardiovascular diseases (CVD) are an important factor in the pathophysiology of type 2 diabetes mellitus (2).…”