Inhibition of advanced glycation end products: An implicit goal in clinical medicine for the treatment of diabetic nephropathy?

Toshio Miyata, Yuko Izuhara

Research output: Chapter in Book/Report/Conference proceedingConference contribution

11 Citations (Scopus)

Abstract

Several factors have been incriminated in the genesis of diabetic nephropathy. To elucidate their interplay, we have used a hypertensive, obese, diabetic rat model with nephropathy (SHR/NDmcr-cp) that mimics human type 2 diabetes. This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal advanced glycation end product (AGE) accumulation. In order to achieve renoprotection, which was evaluated by histology and albuminuria, various therapeutic approaches were used: caloric restriction, antihypertensive agents (angiotensin II receptor blocker [ARB] and calcium channel blocker), lipid- (bezafibrate) or glucose-lowering (insulin and pioglitazone) agents, and cobalt chloride (a hypoxia-inducible factor activator). Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with decreased AGE formation, with the exception of insulin, which induces hyperinsulinemia, eventually leading to an overproduction of transforming growth factor-β. AGE formation is reduced directly by in vitro active compounds (e.g., ARBs) or indirectly by in vitro inactive compounds (e.g., pioglitazone and cobalt). In the latter cases, AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers. It remains to be seen whether the renoprotection offered by these various approaches may be additive.

Original languageEnglish
Title of host publicationThe Maillard Reaction Recent Advances in Food and Biomedical Sciences
PublisherBlackwell Publishing Inc.
Pages141-146
Number of pages6
ISBN (Print)9781573317, 9789781573316
DOIs
Publication statusPublished - 2008 Apr
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1126
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Advanced glycation
  • Blood pressure
  • Chronic hypoxia
  • Diabetic nephropathy
  • Oxidative stress
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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