Background:
The incidence and prevalence of diabetes mellitus are increasing globally at alarming
rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with
diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound – is increased in patients with diabetes
and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications. Derived
from glucose, MG binds to arginine and lysine residues in proteins, and the resultant end products serve as
surrogate markers of MG generation in vivo. Under normal conditions, MG is detoxified by the enzyme glyoxalase
1 (Glo1), using reduced glutathione as a co-factor. Elevated levels of MG is known to cause endothelial and
vascular dysfunction, oxidative stress and atherosclerosis; all of which are risk factors for cardiovascular diseases.
Moreover, MG has also been shown to cause pathologic structural alterations and impair kidney function. Conversely,
MG scavengers (such as N-acetylcysteine, aminoguanidine or metformin) or Nrf2/Glo1 activators (such
as trans-resveratrol / hesperetin) are shown to be useful in preventing MG-induced cardiovascular and renal complications
in diabetes. However, clinical evidence supporting the MG lowering properties of these agents are
limited and hence, need further investigation.
Conclusion:
Reducing MG levels directly using scavengers or indirectly via activation of Nrf2/Glo1 may serve as
a novel and potent therapeutic strategy to counter the deleterious effects of MG in diabetic complications.
A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway
