To investigate the role of glucose transporter (GLUT) 2 and 4 in hyperuricemia-induced insulin resistance.

Male uric acid oxidase gene knock-out spontaneous hyperuricemia mice (KO) and wild-type mice (WT) were fed with high-fat diet to establish an insulin resistance model. Then, some of KO mice were treated with allopurinol for lowering uric acid. Uric acid, fasting plasma glucose (FPG), and fasting insulin (FINS) were detected. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed. Finally, the expression levels of Slc2a4 and Slc2a2 mRNA in tissues were determined by real-time PCR, while those of GLUT2 and GLUT4 proteins in tissues were analyzed by Western blot.

There was no significant difference in FPG among various groups. The level of FINS in KO group was significantly higher than that in WT group [(0.636±0.07) vs (0.456±0.03) ng/ml, P<0.01], with decreased insulin sensitivity and impaired glucose tolerance. The uric acid level in the KO group remained at a high level [(549.68±48.7) vs (216.61±27.5)μmol/L]. After uric acid level in KO mice was reduced by allopurinol, insulin sensitivity and glucose metabolism were improved. Compared with WT group, the expression levels of Slc2a4 and GLUT4 in the gastrocnemius muscle were decreased while the expression levels of Slc2a2 and GLTU2 in liver were increased in KO group, which were reversed by allopurinol-mediated uric acid reduction.

Uric acid may induce insulin resistance via decreasing Slc2a4/GLUT4 expressions in skeletal muscle, and increasing Slc2a2/GLTU2 expressions in liver. (Chin J Endocrinol Metab, 2018, 34: 862-866)

Hyperuricemia; Insulin resistance; Glucose transporter 2; Glucose transporter 4