Increased Urinary TGF-β1 and Cortical Renal GLUT1 and GLUT2 Levels: Additive Effects of Hypertension and Diabetes

Abstract

Background/Aim: Diabetes and mesangial stretch caused by hypertension increase mesangial matrix deposition which is induced by local production of transforming growth factor beta 1 (TGF-β1). Both conditions are associated with cortical GLUT1 overexpression. We evaluated the effect of genetically determined hypertension and its association with diabetes on urinary TGF-β1 and cortical GLUT1 and GLUT2 expression. Methods: We studied Wistar-Kyoto rats (controls, C) and spontaneously hypertensive rats (SHR), weighing ∼210 g, 30 days after the injection of streptozotocin (diabetic, D) or citrate buffer (10 C, 9 SHR, 12 C-D and 15 SHR-D). Twenty-four-hour urine was collected for glucose, albumin, and TGF-β1 determinations. Catheters were implanted into the femoral artery to measure the arterial blood pressure in conscious animals 1 day later. Then GLUT1 and GLUT2 protein levels (Western blotting) in renal cortex and medulla were evaluated. Results: The cortical GLUT1 levels were 5, 2, and 7 times higher in SHR, C-D, and SHR-D groups versus C group (p < 0.05); the GLUT2 contents were 1.5, 1.8, and 2.3 times higher in SHR, C-D and SHR-D groups versus C group (p < 0.05). The urinary TGF-β1 level was elevated by diabetes and diabetes and hypertension, but not by hypertension alone: 1.39 ± 0.2, 2.34 ± 0.6, 18.2 ± 3.2, and 28.8 ± 7.6 ng/24 h, respectively, in C, SHR, C-D, and SHR-D groups (p < 0.05). Conclusions: Diabetes, hypertension, and especially their association increase the renal cortical GLUT1 and GLUT2 levels. The magnitude of GLUT1 overexpression caused by hypertension is higher than that induced by diabetes alone. The impact on urinary TGF-β1 occurs when diabetes and hypertension are associated, suggesting an effect that is triggered in the presence of GLUT1 overexpression and hyperglycemia.