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Therapeutic interruption of advanced glycation in diabetic nephropathy: do all roads lead to Rome?

Karly C Sourris1, Josephine M Forbes, Mark E Cooper

  • 1JDRF Albert Einstein Centre for Diabetes Complications, Diabetes and Metabolism Division, Baker Heart Research Institute, Melbourne, Victoria, Australia.

Annals of the New York Academy of Sciences
|May 2, 2008
PubMed

Insights

Chemically diverse drugs that lower advanced glycation end products (AGEs) protect organs in diabetes. Their exact protective mechanisms, whether AGE reduction or signaling inhibition, require further investigation.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Diabetology

Background:

  • Advanced glycation end products (AGEs) are implicated in diabetic complications.
  • Chemically diverse compounds inhibiting AGEs show organ protection in diabetes models.
  • The precise mechanisms of AGE-lowering therapies remain unclear.

Purpose of the Study:

  • To investigate the mechanisms underlying the organ-protective effects of AGE-lowering therapies.
  • To determine if AGE reduction or downstream signaling inhibition is the primary mode of action.
  • To explore other potential mechanisms like antioxidant stimulation, lipid-lowering, and anti-inflammatory effects.

Main Methods:

  • Review of experimental models of diabetes complications.
  • Analysis of the known actions of AGE-lowering agents.
  • Exploration of the advanced glycation pathway and related signaling.

Main Results:

  • A common feature of effective AGE inhibitors is end-organ protection in diabetes models.
  • The exact mechanisms of these therapies are not fully elucidated.
  • Potential mechanisms include AGE reduction, signaling inhibition, antioxidant effects, lipid modification, and anti-inflammation.

Conclusions:

  • Understanding the diverse actions of AGE-lowering agents is crucial for treating diabetic complications.
  • Further research is needed to elucidate the specific pathways involved.
  • Targeting AGEs and related pathways offers potential therapeutic strategies for diabetes.

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