Dicarbonyls Generation, Toxicities, Detoxifications and Potential Roles in Diabetes Complications

Curr Protein Pept Sci. 2020;21(9):890-898. doi: 10.2174/1389203720666191010155145.

Abstract

It has been well established that advanced glycation end-products (AGEs) have a strong correlation with diabetes and its secondary complications. Moreover, dicarbonyls, especially, methylglyoxal (MG) and glyoxal, accelerate AGEs formation and hence, have potential roles in the pathogenesis of diabetes. They can also induce oxidative stress and concomitantly decrease the efficiency of antioxidant enzymes. Increased proinflammatory cytokines (tumor necrosis factor-α and interleukin- 1β) are secreted by monocytes due to the dicarbonyl-modified proteins. High levels of blood dicarbonyls have been identified in diabetes and its associated complications (retinopathy, nephropathy and neuropathy). This review aims to provide a better understanding by including in-depth information about the formation of MG and glyoxal through multiple pathways with a focus on their biological functions and detoxifications. The potential role of these dicarbonyls in secondary diabetic complications is also discussed.

Keywords: Dicarbonyls; detoxification; diabetic complications; glyoxal; methylglyoxal; toxicity.

Publication types

  • Review

MeSH terms

  • Deoxyglucose / analogs & derivatives*
  • Deoxyglucose / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / genetics
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / pathology
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / genetics
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology
  • Gene Expression Regulation
  • Glycation End Products, Advanced / genetics
  • Glycation End Products, Advanced / metabolism
  • Glyoxal / metabolism*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lactoylglutathione Lyase / genetics
  • Lactoylglutathione Lyase / metabolism
  • Oxidative Stress
  • Protein Carbonylation
  • Pyruvaldehyde / metabolism*
  • Signal Transduction

Substances

  • Glycation End Products, Advanced
  • Insulin
  • Isoenzymes
  • Glyoxal
  • Pyruvaldehyde
  • Deoxyglucose
  • GLO1 protein, human
  • Lactoylglutathione Lyase
  • 3-deoxyglucosone