Protein glycation, diabetes, and aging.

By P. Ulrich, A. Cerami. Recent Progress in Hormone Research, 2001

841 citations recorded by the source corpus.

Biological amines react with reducing sugars to form a complex family of rearranged and dehydrated covalent adducts that are often yellow-brown and/or fluorescent and include many cross-linked structures. Food chemists have long studied this process as a source of flavor, color, and texture changes in cooked, processed, and stored foods. During the 1970s and 1980s, it was realized that this process, called the Maillard reaction or advanced glycation, also occurs slowly in vivo. Advanced glycation endproducts (AGEs) that form are implicated, causing the complications of diabetes and aging, primarily via adventitious and crosslinking of proteins. Long-lived proteins such as structural collagen and lens crystallins particularly are implicated as pathogenic targets of AGE processes. AGE formation in vascular wall collagen appears to be an especially deleterious event, causing crosslinking of collagen molecules to each other and to circulating proteins. This leads to plaque formation, basement membrane thickening, and loss of vascular elasticity. The chemistry of these later-stage, glycation-derived crosslinks is still incompletely understood but, based on the hypothesis that AGE formation involves reactive carbonyl groups, the authors introduced the carbonyl reagent aminoguanidine hydrochloride as an inhibitor of AGE formation in vivo in the mid 1980s. Subsequent studies by many researchers have shown the effectiveness of aminoguanidine in slowing or preventing a wide range of complications of diabetes and aging in animals and, recently, in humans. Since, the authors have developed a new class of agents, exemplified by 4,5-dimethyl-3-phenacylthiazolium chloride (DPTC), which can chemically break already-formed AGE protein-protein crosslinks. These agents are based on a new theory of AGE crosslinking that postulates that alpha-dicarbonyl structures are present in AGE protein-protein crosslinks. In studies in aged animals, DPTC has been shown to be capable of reverting indices of vascular compliance to levels seen in younger animals. Human clinical trials are underway.

Subfields: Clinical Biochemistry

View Paper: https://www.semanticscholar.org/paper/513cfa91ca2bba19485640d4ad87d30660959b27

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In Clinical Biochemistry

1. C. Palmeira
2. A. Rolo
3. S. Salim

Citations in the corpus

• Trends in oxidative aging theories. (2007, background): “Considering the high rates of flux through glycolysis in yeast, ensuing production of reactive aldehydes such as methyglyoxal (leaked from triosephosphate isomerase [57,58]) and the clonal aging-related increase in protein carbonyls [43], we suggest that advanced glycation end products [59,60] may p”
• Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet (2010, background): “The formation of AGEs is a part of normal metabolism, but if excessively high levels of AGEs are reached in tissues and the circulation they can become pathogenic (2).”
• Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing (2012, background): “This finding indicates that AGEs play key pathophysiological roles in increasing oxidative stress in diabetes along with subsequent endothelial dysfunction through decreasing endothelial nitric oxide synthase (eNOS) phosphorylation.”
• Diabetes associated cell stress and dysfunction: role of mitochondrial and non‐mitochondrial ROS production and activity (2007, background): “However, the rearrangement of the Schiff base is much faster, originating an Amadori product (Ulrich & Cerami, 2001).”
• Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. (2006, background): “This reaction, which is believed to occur via an intermediate, open chain enol form, is much faster than the reverse reaction (Ulrich and Cerami, 2001).”
• Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. (2005, background): “Based on extensive preclinical efficacy in animal models in which AGEs are prevalent (Edelstein and Brownlee, 1992; Ulrich and Cerami, 2001), pimagedine was administered to 690 subjects with type 1 diabetes, nephropathy, and retinopathy.”