Dicarbonyl-mediated AGEing and diabetic kidney disease

Alexandra Dimitropoulos, Carlos J. Rosado, Merlin C. Thomas

Research output: Contribution to journalReview ArticleOtherpeer-review

5 Citations (Scopus)

Abstract

Increased glycolytic flux into the diabetic kidney, combined with glycolytic inefficiencies introduced by oxidative stress, acts to increase the generation of triose-phosphate intermediates, which spontaneously degrade to form methylglyoxal. At the same time, the glyoxalase-catalysed pathway that degrades excess methylglyoxal is impaired. The resulting dicarbonyl stress increases the accumulation of Advanced Glycation End-products (AGEs), as highly reactive dicarbonyls modify proteins, DNA, phospholipids and even small molecules like glutathione and nitric oxide. The resulting molecular dysfunction, contributes to the development and progression of kidney disease in diabetes. The importance of the dicarbonyls in diabetic kidney disease is clearly demonstrated by the reno-protective benefits of structurally-disparate dicarbonyl scavengers in experimental studies. Equally, modulating the glyoxalase pathway is able to alter both dicarbonyl generation and renal dysfunction in the presence and absence of hyperglycaemia. However, beyond improving glycemia control and reducing oxidative stress, an effective way to attenuate dicarbonyl-mediated damage in patients with diabetic kidney disease remains an elusive goal.

Original languageEnglish
Number of pages7
JournalJournal of Nephrology
DOIs
Publication statusAccepted/In press - 13 Mar 2020

Keywords

  • Advanced glycation end-products
  • AGEs dicarbonyl
  • Diabetic kidney disease
  • DKD
  • GLO1
  • Glyoxalase
  • Methylglyoxal
  • MG
  • RAGE
  • Receptor for advanced glycation end-products

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