Objective: Persons with type 2 diabetes have increased incidence of hyperuricemia and gout. The hypothesis that Urate transporter 1 (URAT1) levels are increased in type 2 diabetic Zucker rats and this is responsible f...Objective: Persons with type 2 diabetes have increased incidence of hyperuricemia and gout. The hypothesis that Urate transporter 1 (URAT1) levels are increased in type 2 diabetic Zucker rats and this is responsible for elevation of uric acid was tested. Methods: Male 12-week-old obese Zucker rats were compared to non-diabetic lean counterparts. Plasma glucose, uric acid and creatinine were measured. URAT1 protein levels in the renal cortex and medulla were determined by Western blot. Immunohistochemistry was used to determine the location of URAT1 inrenal tubules. Results: Plasma glucose and uric acid levels were higher in the diabetic rats. There was no difference in plasma createnine. URAT1 antibody-positive bands of 27, 31, 50, 62 and 70 kDa were observed in cortex. A similar pattern was observed in medulla with addition of a 44 kDa band. No differences were observed in URAT1 proteins in the cortex between obese and lean rats. In the medulla, expression of the 44 and 50 kDa proteins was higher in lean rats. Expression of 27, 50, 62 kDa URAT1 proteins in the cortex was higher than in the medulla, while expression of the 70 kDa URAT1 was higher in medulla than in cortex. Localization of URAT1 did not differ between groups and included tubules in both cortex and medulla. Conclusions: In male Zucker rats, URAT1 protein expression was observed in both kidney cortex and medulla. Uric acid elevation in the obese group was associated with decreases in the 44 and 50 kDa URAT1 proteins in renal medulla.展开更多
文摘Objective: Persons with type 2 diabetes have increased incidence of hyperuricemia and gout. The hypothesis that Urate transporter 1 (URAT1) levels are increased in type 2 diabetic Zucker rats and this is responsible for elevation of uric acid was tested. Methods: Male 12-week-old obese Zucker rats were compared to non-diabetic lean counterparts. Plasma glucose, uric acid and creatinine were measured. URAT1 protein levels in the renal cortex and medulla were determined by Western blot. Immunohistochemistry was used to determine the location of URAT1 inrenal tubules. Results: Plasma glucose and uric acid levels were higher in the diabetic rats. There was no difference in plasma createnine. URAT1 antibody-positive bands of 27, 31, 50, 62 and 70 kDa were observed in cortex. A similar pattern was observed in medulla with addition of a 44 kDa band. No differences were observed in URAT1 proteins in the cortex between obese and lean rats. In the medulla, expression of the 44 and 50 kDa proteins was higher in lean rats. Expression of 27, 50, 62 kDa URAT1 proteins in the cortex was higher than in the medulla, while expression of the 70 kDa URAT1 was higher in medulla than in cortex. Localization of URAT1 did not differ between groups and included tubules in both cortex and medulla. Conclusions: In male Zucker rats, URAT1 protein expression was observed in both kidney cortex and medulla. Uric acid elevation in the obese group was associated with decreases in the 44 and 50 kDa URAT1 proteins in renal medulla.
