Glucosepane

A poorly understood advanced glycation end product of growing importance for diabetes and its complications

Vincent M. Monnier, Wanjie Sun, David R. Sell, Xingjun Fan, Ina Nemet, Saul Genuth

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Advanced glycation end products (AGEs) represent a family of protein, peptide, amino acid, nucleic acid and lipid adducts formed by the reaction of carbonyl compounds derived directly or indirectly from glucose, ascorbic acid and other metabolites such as methylglyoxal. AGE formation in diabetes is of growing importance for their role as markers and potential culprits of diabetic complications, in particular retinopathy, nephropathy and neuropathy. Development of sensitive and specific assays utilizing liquid chromatography mass spectrometry with isotope dilution method has made it possible to detect and quantitate non-UV active AGEs such as carboxymethyllysine and glucosepane, the most prevalent AGE and protein crosslink of the extracellular matrix. Below we review studies on AGE formation in two skin biopsies obtained near the closeout of the Diabetes Control and Complications Trial (DCCT), one of which was processed in 2011 for assay of novel AGEs. The results of these analyses show that while several AGEs are associated and predict complication progression, the glucose/fructose-lysine/glucosepane AGE axis is one of the most robust markers for microvascular disease, especially retinopathy, in spite of adjustment for past or future average glycemia. Yet overall little biological and clinical information is available on glucosepane, making this review a call for data in a field of growing importance for diabetes and chronic metabolic diseases of aging.

Original languageEnglish (US)
Pages (from-to)21-32
Number of pages12
JournalClinical Chemistry and Laboratory Medicine
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Diabetes Complications
Medical problems
Assays
Amino Acids, Peptides, and Proteins
Pyruvaldehyde
Glucose
Carbonyl compounds
Biopsy
Extracellular Matrix Proteins
Metabolic Diseases
Liquid chromatography
Metabolites
Liquid Chromatography
Isotopes
Nucleic Acids
Dilution
Ascorbic Acid
Mass spectrometry
Mass Spectrometry

Keywords

  • carbonyl stress
  • glycemia
  • HbA
  • methyglyoxal
  • nephropathy
  • neuropathy
  • retinopathy

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Glucosepane : A poorly understood advanced glycation end product of growing importance for diabetes and its complications. / Monnier, Vincent M.; Sun, Wanjie; Sell, David R.; Fan, Xingjun; Nemet, Ina; Genuth, Saul.

In: Clinical Chemistry and Laboratory Medicine, Vol. 52, No. 1, 01.01.2014, p. 21-32.

Research output: Contribution to journalReview article

Monnier, Vincent M. ; Sun, Wanjie ; Sell, David R. ; Fan, Xingjun ; Nemet, Ina ; Genuth, Saul. / Glucosepane : A poorly understood advanced glycation end product of growing importance for diabetes and its complications. In: Clinical Chemistry and Laboratory Medicine. 2014 ; Vol. 52, No. 1. pp. 21-32.
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