Low-molecular weight advanced glycation end products: Markers of tissue AGE accumulation and more?

Merlin C. Thomas, Josephine M. Forbes, Richard MacIsaac, George Jerums, Mark E. Cooper

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

Incomplete digestion of advanced glycation end product (AGE)-modified protein results in the formation of low-molecular weight degradation products incorporating AGE modifications (LMW-AGEs). In addition to being biomarkers of AGE modification, LMW-AGEs may have a high toxic potential, being free to interact with AGE receptors at distant sites via the circulation. Several free AGEs have been identified, including pentosidine, Nε- (carboxymethyl)lysine (CML), and free-imidazole AGEs. In addition, fluorescence (370 nm [excitation]/440 nm [emission]) in the LMW phase of serum correlates with tissue fluorescence, an established marker for AGE modification. In experimental diabetes, LMW fluorescence increases with duration of disease and is normalized with the AGE inhibitor aminoguanidine. LMW fluorescence is also higher in patients with diabetes, in whom it is associated with glomerular filtration rate and hemoglobin. Patients with hyperfiltration have lower LMW fluorescence than those with normal renal function, which may protect them from AGE accumulation in the short term. These findings provide clinical support for the association between AGEs and progressive renal injury in diabetes.

Original languageEnglish
Pages (from-to)644-654
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1043
DOIs
Publication statusPublished - 1 Jan 2005
Externally publishedYes

Keywords

  • Advanced glycation end products (AGEs)
  • Anemia
  • Diabetes
  • Diabetic nephropathy
  • Fluorescence

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