Metabolic and cardiovascular effects of chronic mild hyperuricemia in rodents

Sun K. Park, Tara R. Rosenthal, Jessica S. Williams, John M. Shelton, Masaya Takahashi, Shanrong Zhang, Ion Alexandru Bobulescu

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1 Scopus citations

Abstract

Mildly elevated serum uric acid levels are common in people with metabolic syndrome and type 2 diabetes mellitus (T2DM), but whether elevated uric acid has a causal role in the pathogenesis of diabetes remains uncertain. We tested whether chronic mild hyperuricemia in rodents under controlled laboratory conditions can cause glucose intolerance in otherwise healthy animals, or whether it can worsen glucometabolic control in animals that are genetically predisposed to T2DM. We used an established model of experimental hyperuricemia in rodents with potassium oxonate dietary supplementation, which led to sustained, approximately two-fold elevation of uric acid compared with control animals. We also reversed the hyperuricemic effect of oxonate in some animals by treatment with a xanthine oxidase inhibitor. Manipulation of serum uric acid levels in Sprague-Dawley rats for up to 18 weeks did not affect fasting glucose and glucose tolerance. Blood pressure was also not affected by hyperuricemia in rats fed a Western-Type diet. We next sought to determine whether uric acid may aggravate or accelerate the onset of glucometabolic abnormalities in rats already predisposed to T2DM. Chronic oxonate treatment in Zucker diabetic fatty (ZDF) and lean control rats for up to 6 weeks did not affect fasting glucose, insulin, and glucose tolerance in ZDF rats. Taken together, these findings indicate that elevated uric acid does not directly contribute to the pathogenesis of glucose intolerance and T2DM in rodents.

Original languageEnglish (US)
Pages (from-to)1037-1044
Number of pages8
JournalJournal of Investigative Medicine
Volume66
Issue number7
DOIs
StatePublished - Oct 2018

Keywords

  • diabetes mellitus
  • hypertension
  • rats

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Park, S. K., Rosenthal, T. R., Williams, J. S., Shelton, J. M., Takahashi, M., Zhang, S., & Bobulescu, I. A. (2018). Metabolic and cardiovascular effects of chronic mild hyperuricemia in rodents. Journal of Investigative Medicine, 66(7), 1037-1044. https://doi.org/10.1136/jim-2018-000729