Diabetic threesome (hyperglycemia, renal function and nutrition) and advanced glycation end products: evidence for the multiple-hit agent?
| Authors | |
|---|---|
| Year of publication | 2008 |
| Type | Article in Periodical |
| Magazine / Source | Proceedings of the Nutrition Society |
| MU Faculty or unit | |
| Citation | |
| Field | Endocrinology, diabetology, metabolism, nutrition |
| Keywords | AGEs; diabetes mellitus; diabetic nephropathy; fructosamine 3 kinase; glycation; glyoxalase; nutrigenetics; RAGE |
| Description | Complex chemical processes called non-enzymatic glycation operating in vivo and analogical chemical interactions between sugars and proteins occurring during thermal processing of food (know se Maillard reaction) are one of the interesting examples of potentially harmful interaction between nutrition and disease. Non-enzymatic glycation comprise a series of reactions between sugars, alpha-oxoaldehydes and other sugar derivatives and amino groups of amino acids, peptides and proteins leading to the formation of heterogeneous moieties collectively called Advanced Glycation End-products (AGEs). AGEs possess a wide range of chemical and biological properties and play a role in diabetes-related pathology as wells as in several other diseases. Diabetes is, nevertheless, of main interest for several reasons: (i) chronic hyperglycemia feeds the substrates for the extra- as well as intracellular glycation, (ii) hyperglycaemia-induced oxidative stress accelerates AGE formation in the process of glycoxidation, (iii) AGE-modified proteins are subjects of rapid intracellular proteolytic degradation releasing free AGE-adducts into the circulation where they can bind to several pro-inflammatory receptors, especially Receptor of AGEs (RAGE), and, finally, (iv) kidneys, which are principally involved in the excretion of free AGE-adducts, might be damaged by diabetic nephropathy and this further enhances AGE-toxicity because of diminished AGE clearance. Increased dietary intake of AGEs in highly processed foods might represent an additional, exogenous, metabolic burden on top of those already present endogenously in diabetics. Finally, interindividual genetic and functional variability in genes encoding enzymes and receptors involved in either formation or degradation of AGEs could have a significant pathogenic, nutrigenomic and nutrigenetic consequences. |
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