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Current Molecular Medicine

Eiditor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

TAGE (Toxic AGEs) Theory in Diabetic Complications

Author(s): Takashi Sato, Mina Iwaki, Noriko Shimogaito, Xuegang Wu, Sho-ichi Yamagishi and Masayoshi Takeuchi

Volume 6 , Issue 3 , 2006

Page: [351 - 358] Pages: 8

DOI: 10.2174/156652406776894536

Price: $58

Abstract

Diabetic complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis. Chronic hyperglycemia is initially involved in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic derangements. High glucose increased production of various types of advanced glycation endproducts (AGEs). Recently, we found that glyceraldehyde-derived AGEs (AGE-2) play an important role in the pathogenesis of angiopathy in diabetic patients. There is considerable interest in receptor for AGEs (RAGE) found on many cell types, particularly those affected in diabetes. Recent studies suggest that interaction of AGE-2 (predominantly structure of toxic AGEs; TAGE) with RAGE alters intracellular signaling, gene expression, release of pro-inflamatory molecules and production of reactive oxygen species (ROS) that contribute towards the pathology of diabetic complications. We propose three pathways for the in vivo formation of AGE-2 precursor, glyceraldehyde, such as i) glycolytic pathway, ii) polyol pathway, and iii) fructose metabolic pathway. Glyceraldehyde can be transported or can leak passively across the plasma membrane. It can react non-enzymatically with proteins to lead to accelerated formation of TAGE at both intracellularly and extracellularly. In this review, we discuss the molecular mechanisms of diabetic complications, especially focusing on toxic AGEs (TAGE) and their receptor (RAGE) system.

Keywords: Advanced glycation end-products (AGEs), glyceraldehyde-derived AGEs (AGE-2), receptor for AGEs (RAGE), diabetic complications, retinopathy, nephropathy, neuropathy


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