503-P: Inhibition of Glucose Transporter 9 Increases Serum Uric Acid Level but Attenuates Renal Albumin Excretion in Streptozotocin-Induced Diabetic Rats: A Role of Hepatic Uric Acid Metabolism

Abstract

Background: In previous studies, we confirmed that endogenous uric acid (UA) formation increases in the streptozotocin (STZ)-induced diabetic rats with renal injury. Yet changes of renal UA reabsorption and hepatic UA metabolism remain unclear in this model. Methods: STZ-induced diabetic rats and control rats were treated with benzbromarone (BZ), a glucose transporter 9 (GLUT9) inhibitor for 8 weeks. At baseline, 4 and 8 weeks after BZ treatment, blood samples were collected for fasting blood glucose (FBG), serum uric acid (SUA), serum creatinine (SCr), and blood urea nitrogen (BUN). Simultaneous urinary samples were tested and daily urinary amount of albumin (UAE), uric acid (UUA), creatinine (UCR), urea nitrogen (UUN) were calculated. Gene expressions of GLUT9, xanthine oxidase (XO), urate transporter 1 (URAT1) in the kidney and GLUT9, XO as well as uricase in the liver were detected by RT-PCR. Results: 1) Compared with normal rats, FBG, BUN, UUN, UAE and UUA were significantly increased, while SUA was significantly decreased in diabetic rats, while SCr and UCR levels were compared. Treatment with BZ did not change FBG in both rats. BZ significantly decreased SCr, BUN and UAE levels but increased SUA in diabetic rats. 2) In the kidney, expression of GLUT9 and XO was increased, while URAT1 was not altered in diabetic rats if compared with control rats. BZ treatment exerted no any effects on gene expression of GLUT9 and XO. 3) In the liver, gene expression of XO and uricase was compared between diabetic and normal rats, while GLUT9 was significantly upregulated in diabetic rats. BZ treatment remarkably inhibited GLUT9 expression but left XO and uricase unchanged in diabetic rats. Conclusions: 1) Inhibition of hepatic GLUT9 in STZ-induced diabetic rats increased SUA indicates that GLUT9 pathway for UA metabolism is critical in this model. 2) BZ treatment attenuates urinary albumin excretion in diabetes. Disclosure C. Chen: None. J. Ran: None. R. Zhang: None. G. Chen: None. P. Zhu: None. J. Qiu: None. R. Tan: None. Y. Liu: None.