Role of glucose transporter 2 and 4 in insulin resistance in spontaneous hyperuricemia mice
10.3760/cma.j.issn.1000-6699.2018.10.011
- VernacularTitle:葡萄糖转运蛋白2和4在自发高尿酸血症小鼠发生胰岛素抵抗中的作用
- Author:
Xiaojie QU
1
;
Xueshan BAI
;
Xiuying WU
;
Zhen LIU
;
Changgui LI
Author Information
1. 山东省代谢性疾病重点实验室
- Keywords:
Hyperuricemia;
Insulin resistance;
Glucose transporter 2;
Glucose transporter 4
- From:
Chinese Journal of Endocrinology and Metabolism
2018;34(10):862-866
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of glucose transporter ( GLUT ) 2 and 4 in hyperuricemia-induced insulin resistance. Methods 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. Results 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. Conclusion Uric acid may induce insulin resistance via decreasing Slc2a4/GLUT4 expressions in skeletal muscle, and increasing Slc2a2/GLTU2 expressions in liver.
