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Glyoxalase in diabetes, obesity and related disorders
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Rabbani, Naila and Thornalley, Paul J. (2011) Glyoxalase in diabetes, obesity and related disorders. Seminars in Cell and Developmental Biology, Vol.22 (No.3). pp. 309-317. doi:10.1016/j.semcdb.2011.02.015 ISSN 1084-9521.
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Official URL: http://dx.doi.org/10.1016/j.semcdb.2011.02.015
Abstract
Diabetes was the first disease state where evidence emerged for increased formation of methylglyoxal. Metabolism of methylglyoxal by the glyoxalase system has been linked to the development of vascular complications of diabetes - nephropathy, retinopathy, neuropathy and cardiovascular disease. Increased formation of methylglyoxal in hyperglycaemia associated with diabetes and down regulation of glyoxalase 1 by inflammatory signalling in vascular cells leads to a marked increased modification of proteins by methylglyoxal to form advanced glycation endproducts at the sites of vascular complications. Hotspot protein targets of methylglyoxal that suffer functional impairment - the dicarbonyl proteome - likely play a key role in the mechanisms underlying the development of vascular complications in diabetes: particularly modification of integrin binding sites in extracellular matrix proteins leading to endothelial cell shedding and anoikis, modification of mitochondrial proteins and increased formation of reaction oxygen species, and modification of apolipoprotein B100 of low density lipoprotein leading to its increased atherogenicity. Some current therapeutic agents counter partially dysfunctional metabolism of methylglyoxal by the glyoxalase system in diabetes - including the recent development of high dose thiamine therapy for early stage diabetic nephropathy. Further pharmacologic strategies are required to overcome the down regulation of glyoxalase1 in diabetes. The glyoxalase system is likely to be a continuing and future focus for research on clinical biomarkers and therapeutic development for respectively assessment of metabolic control and prevention of vascular complications in diabetes and obesity. (C) 2011 Elsevier Ltd. All rights reserved.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > R Medicine (General) | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Seminars in Cell and Developmental Biology | ||||
| Publisher: | Elsevier Science Ltd. / Academic Press Ltd. | ||||
| ISSN: | 1084-9521 | ||||
| Official Date: | May 2011 | ||||
| Dates: |
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| Volume: | Vol.22 | ||||
| Number: | No.3 | ||||
| Page Range: | pp. 309-317 | ||||
| DOI: | 10.1016/j.semcdb.2011.02.015 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Diabetes UK , British Heart Foundation (BHF) |
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