Role of advanced glycosylation products in complications of diabetes

A. Cerami, H. Vlassara, M. Brownlee

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Glucose and other reducing sugars can react with proteins and nucleic acids, without the aid of enzymes, to form stable covalent adduct. These reactions, although studied by food chemists, have recently been found to occur in vivo. This has led to studies on the accumulation of these advanced glycosylation end products (AGE) and the role it plays in the aging of long-lived proteins and nucleic acids. In contrast to the Amadori product, which is in equilibrium with glucose, AGE is irreversibly attached to the proteins. The AGE moieties are brown, fluorescent chromophores that can cross-link proteins. We have identified and characterized two specific AGE glucose-derived cross-links in proteins 2-furoyl-4(5)-(2-furanyl)-1H-imidazole (FFI) and 1-alkyl-2-formyl-3,4-diglycosylpyrrole (AFGP). By use of a radioimmunoassay for FFI identification, it has been possible to demonstrate the presence of FFI in situ in proteins that had been exposed to glucose in vitro and in vivo. Recently, we found that reducing sugars react with amino groups of DNA nucleotides in a manner analogous to the nonenzymatic glycosylation of amino groups on proteins. The AGE-DNA formed in this manner has spectral and fluorescent properties similar to those of AGE-proteins. We have observed that formation of AGE on DNA decreases the ability of the single-stranded virus f1 to transfect Escherichia coli. When the plasmid pBR322 containing ampicillin- and tetracycline-resistant genes is incubated with reducing sugars, specific mutations are observed. These mutations have been found to be caused by insertions and deletions of the DNA. Further studies are needed for measuring the amounts of AGE-DNA and proteins linked to DNA by AGE. Potential mechanisms for repair of AGE-DNA also needs to be explored further. These studies will give insight into the possible role of glucose as an important mediator of aging.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalDiabetes Care
Volume11
Issue numberSUPPL. 1
StatePublished - 1988
Externally publishedYes

Fingerprint

Advanced Glycosylation End Products
Diabetes Complications
Glycosylation
DNA
Glucose
Proteins
Nucleic Acids
Antifreeze Proteins
Mutation
Ampicillin
Tetracycline
Radioimmunoassay
Plasmids
Nucleotides
Escherichia coli
Viruses
Food

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Cerami, A., Vlassara, H., & Brownlee, M. (1988). Role of advanced glycosylation products in complications of diabetes. Diabetes Care, 11(SUPPL. 1), 73-79.

Role of advanced glycosylation products in complications of diabetes. / Cerami, A.; Vlassara, H.; Brownlee, M.

In: Diabetes Care, Vol. 11, No. SUPPL. 1, 1988, p. 73-79.

Research output: Contribution to journalArticle

Cerami, A, Vlassara, H & Brownlee, M 1988, 'Role of advanced glycosylation products in complications of diabetes', Diabetes Care, vol. 11, no. SUPPL. 1, pp. 73-79.
Cerami A, Vlassara H, Brownlee M. Role of advanced glycosylation products in complications of diabetes. Diabetes Care. 1988;11(SUPPL. 1):73-79.
Cerami, A. ; Vlassara, H. ; Brownlee, M. / Role of advanced glycosylation products in complications of diabetes. In: Diabetes Care. 1988 ; Vol. 11, No. SUPPL. 1. pp. 73-79.
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