PMID- 30042113
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20200306
IS  - 1708-8267 (Electronic)
IS  - 1081-5589 (Print)
IS  - 1081-5589 (Linking)
VI  - 66
IP  - 7
DP  - 2018 Oct
TI  - Metabolic and cardiovascular effects of chronic mild hyperuricemia in rodents.
PG  - 1037-1044
LID - 10.1136/jim-2018-000729 [doi]
AB  - 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.
CI  - (c) American Federation for Medical Research (unless otherwise stated in the text 
      of the article) 2018. All rights reserved. No commercial use is permitted unless 
      otherwise expressly granted.
FAU - Park, Sun K
AU  - Park SK
AD  - The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, 
      Dallas, Texas, USA.
FAU - Rosenthal, Tara R
AU  - Rosenthal TR
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Williams, Jessica S
AU  - Williams JS
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
FAU - Shelton, John M
AU  - Shelton JM
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
AD  - Department of Pathology, University of Texas Southwestern Medical Center, Dallas, 
      Texas, USA.
FAU - Takahashi, Masaya
AU  - Takahashi M
AD  - Department of Radiology, University of Texas Southwestern Medical Center, Dallas, 
      Texas, USA.
AD  - The Advanced Imaging Research Center, University of Texas Southwestern Medical 
      Center, Dallas, Texas, USA.
FAU - Zhang, Shanrong
AU  - Zhang S
AD  - The Advanced Imaging Research Center, University of Texas Southwestern Medical 
      Center, Dallas, Texas, USA.
FAU - Bobulescu, Ion Alexandru
AU  - Bobulescu IA
AD  - The Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, 
      Dallas, Texas, USA.
AD  - Department of Internal Medicine, University of Texas Southwestern Medical Center, 
      Dallas, Texas, USA.
LA  - eng
GR  - K01 DK090282/DK/NIDDK NIH HHS/United States
GR  - P30 DK079328/DK/NIDDK NIH HHS/United States
GR  - R01 DK113377/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180724
PL  - England
TA  - J Investig Med
JT  - Journal of investigative medicine : the official publication of the American 
      Federation for Clinical Research
JID - 9501229
RN  - 0 (Blood Glucose)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Blood Pressure
MH  - Body Weight
MH  - Cardiovascular Diseases/blood/*complications/physiopathology
MH  - Chronic Disease
MH  - Fasting/blood
MH  - Fibrosis
MH  - Glucose Tolerance Test
MH  - Heart Function Tests
MH  - Hyperuricemia/blood/*complications/*metabolism/physiopathology
MH  - Kidney/pathology
MH  - Male
MH  - Rats, Sprague-Dawley
MH  - Rats, Zucker
MH  - Thinness/blood
MH  - Uric Acid/blood
PMC - PMC6508882
MID - NIHMS1018307
OTO - NOTNLM
OT  - diabetes mellitus
OT  - hypertension
OT  - rats
COIS- Competing interests: This work was supported in part by an Investigator Initiated 
      Sponsored Research (IISR) grant from Takeda Pharmaceuticals USA (Takeda) to IAB. 
      This grant provided one study drug (Febuxostat) free of charge for animal 
      experiments, as well as research costs that were paid directly to the University 
      of Texas Southwestern Medical Center. Takeda did not provide honoraria, fees, 
      travel costs, or any other form of payment to the study investigators and had no 
      role (direct or indirect) in study design, data collection and analysis, 
      preparation of the manuscript, or decision to publish. The authors have no other 
      conflicts of interest to disclose.
EDAT- 2018/07/26 06:00
MHDA- 2019/10/01 06:00
PMCR- 2019/10/01
CRDT- 2018/07/26 06:00
PHST- 2018/05/02 00:00 [accepted]
PHST- 2018/07/26 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/07/26 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - jim-2018-000729 [pii]
AID - 10.1136/jim-2018-000729 [doi]
PST - ppublish
SO  - J Investig Med. 2018 Oct;66(7):1037-1044. doi: 10.1136/jim-2018-000729. Epub 2018 
      Jul 24.