Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic vascular disease

George Jerums, Sianna Panagiotopoulos, Josephine Forbes, Tanya Osicka, Mark Cooper

Research output: Contribution to journalReview ArticleResearchpeer-review

76 Citations (Scopus)

Abstract

Advanced glycation endproducts (AGEs) have been postulated to play a role in the development of both nephropathy and large vessel disease in diabetes. However, it is still not clear which AGE subtypes play a pathogenetic role and which of several AGE receptors mediate AGE effects on cells. This review summarises the renoprotective effect of inhibitors of AGE formation, including aminoguanidine, and of cross-link breakers, including ALT-711, on experimental diabetic nephropathy and on mesenteric vascular hypertrophy. It also demonstrates similar effects of aminoguanidine and ramipril (an angiotensin converting enzyme inhibitor) on fluorescent and immunoassayable AGE levels, renal protein kinase C activity, nitrotyrosine expression, lysosomal function, and protein handling in experimental diabetes. These findings indicate that inhibition of the renin angiotensin system blocks both upstream and downstream pathways leading to tissue injury. We postulate that the chemical pathways leading to advanced glycation endproduct formation and the renin angiotensin systems may interact through the generation of free radicals, induced both by glucose and angiotensin II. There is also evidence to suggest that AGE-dependent pathways may play a role in the development of tubulointerstitial fibrosis in the diabetic kidney. This effect is mediated through RAGE and is TGF-β and CTGF-dependent.

Original languageEnglish
Pages (from-to)55-62
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume419
Issue number1
DOIs
Publication statusPublished - 1 Nov 2003
Externally publishedYes

Keywords

  • AGEs
  • Albuminuria
  • ALT-711
  • Aminoguanidine
  • Diabetic nephropathy
  • Oxidative stress
  • Protein kinase C
  • Streptozotocin

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