Purine Metabolite Signatures and Type 2 Diabetes: Innocent Bystanders or Actionable Items?

Abstract

PURPOSE OF REVIEW:

This article reviews evidence linking cardiometabolic conditions with changes in purine metabolites, including increased serum uric acid (sUA), and discusses intervention studies that investigated the therapeutic relevance of these associations.

RECENT FINDINGS:

Metabolic and epidemiological findings support a correlation between sUA and circulating levels of other purines with insulin resistance (IR) and risk factors for cardiovascular disease (CVD). In addition, increased activity of xanthine oxidoreductase (XOR), the rate-limiting enzyme for UA production, has been detected in tissues targeted by obesity. Yet, inhibition of XOR in pre-clinical and clinical studies generally failed to support a causal role for excess sUA in IR and CVD. The lack of efficacy of XOR inhibitors strongly suggests that UA is a marker of, rather than a direct contributory factor for, cardiometabolic diseases. Validation of the function of other purines will require a paradigm shift, from a "UA-centric" view to a more granular assessment of the entire purine network and its interaction with other pathways.

• Authors: Giulio R Romeo, Meenu Jain
• Journal: Current diabetes reports (Curr Diab Rep) Vol. 20 Issue 8 Pg. 30 (06 10 2020) ISSN: 1539-0829 [Electronic] United States
• PMID: 32519009 (Publication Type: Journal Article, Review)

Chemical References

• Purines
• Uric Acid
• Xanthine Dehydrogenase
• purine

Topics

• Diabetes Mellitus, Type 2 (epidemiology)
• Humans
• Purines
• Uric Acid
• Xanthine Dehydrogenase