Impact of rosiglitazone on uric acid metabolism and its mechanism

Objective To observe whether high-level insulin increases serum uric acid level and rosiglitazone improves hyperuricemia, and to explore the mechanism. Methods OLETF rats with spontaneous type 2 diabetes complicated with metabolic syndrome and normal control LETO rats were randomly divided into three groups (n=20 each). The animals were fed with standard chow diet in control group, high-purine diet and adenine administered intragastrically in experimental group, and rosiglitazone in interventional group. Body weight, serum levels of uric acid, insulin, triglyceride ( TG ) , and total cholesterol ( TC ) were measured after 3 weeks. Urate transporter 1 ( URAT1 ) and uric acid transporter (UAT) mRNA expressions in renal cortex were examined. HK-2 cells were incubated with various concentrations of insulin for 24 hours. UAT mRNA expression in HK-2 cells was examined. Results ( 1 ) In control group, the insulin level of OLETF rats was significantly higher than that of LETO rats ( P<0. 05 ), and there was no significant difference in serum uric acid level between OLETF and LETO rats. (2)In experimental groups, the insulin level in OLETF rats was significantly higher than that in LETO rats [(61.83±12.13 vs 36.73±12.73 )μIU/ml ,P<0. 05], and the incidence of hyperuricemia (76.92% vs 36.13%,P<0.01 ) and serum uric acid level[( 327.75 ±45.73 vs 264.40±36.32 ) μmol/L, P<0. 01]in OLETF rats were significantly higher than those in LETO rats. (3) Insulin[(41.3± 10.2 vs 61.8±12. 1 )μIU/ml,P<0. 05]and uric acid[( 198.0±45.4 vs 236.9±29.30 ) μmol/L, P<0. 05]levels in OLETF rats in interventional group were significantly lower than those of OLETF rats in experimental group, meanwhile the amount of urinary uric acid excretion was significantly increased[(5 644±371 vs 4 692±278 ) μ mol/L, P<0. 05]. (4) There was no significant difference in insulin level and the expressions of URAT1 and UAT mRNA in renal cortex between OLETF rats in control group and experimental group. URAT1 mRNA expression of OLETF rats in interventional group was significantly decreased, while UAT mRNA expression was significantly increased. (5)With the increase of insulinconcentration in culture medium, the expression of UAT mRNA expression in HK-2 cells was gradually decreased. Conclusions Rosiglitazone may alleviate hyperinsulinemia-induced hyperuricemia via regulating UAT and URAT1 mRNA expression. Key words: Rosiglitazone;  Insulin;  Hyperuricemia;  Urate transporter 1;  Uric acid transporter