METHYLGLYOXAL, A HIGHLY REACTIVE DICARBONYL COMPOUND, IN DIABETES, ITS VASCULAR COMPLICATIONS, AND OTHER AGE-RELATED DISEASES

C. G. Schalkwijk*, C. D. A. Stehouwer

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

149 Citations (Web of Science)

Abstract

The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of nonenzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation end products (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. In this review we summarize the formation of MGO, the detoxification of MGO by the glyoxalase system, and the biochemical pathways through which MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases. Although interventions to treat MGO-associated complications are not yet available in the clinical setting, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Targeting MGO burden may provide new therapeutic applications to mitigate diseases in which MGO plays a crucial role.

Original languageEnglish
Pages (from-to)407-461
Number of pages55
JournalPhysiological Reviews
Volume100
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • advanced glycation end products
  • ageing
  • glyoxalase
  • methylglyoxal
  • obesity
  • type 2 diabetes mellitus
  • GLYCATION END-PRODUCTS
  • GLYOXALASE-I OVEREXPRESSION
  • NITRIC-OXIDE SYNTHASE
  • COPY-NUMBER VARIATION
  • HUMAN SERUM-ALBUMIN
  • BROMOBENZYLGLUTATHIONE CYCLOPENTYL DIESTER
  • INDUCED MITOCHONDRIAL DYSFUNCTION
  • INCIDENT CARDIOVASCULAR-DISEASE
  • RENIN-ANGIOTENSIN-ALDOSTERONE
  • ENDOTHELIAL-CELL METABOLISM

Cite this