title: Increased urinary TGF-beta1 and cortical renal GLUT1 and GLUT2 levels: additive effects of hypertension and diabetes.
abstract: OBJECTIVE
  Diabetes and mesangial stretch caused by hypertension increase mesangial matrix deposition which is induced by local production of transforming growth factor beta 1 (TGF-beta1). Both conditions are associated with cortical GLUT1 overexpression. We evaluated the effect of genetically determined hypertension and its association with diabetes on urinary TGF-beta1 and cortical GLUT1 and GLUT2 expression.
  
  
  METHODS
  We studied Wistar-Kyoto rats (controls, C) and spontaneously hypertensive rats (SHR), weighing approximately 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-beta1 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-beta1 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-beta1 occurs when diabetes and hypertension are associated, suggesting an effect that is triggered in the presence of GLUT1 overexpression and hyperglycemia.
authors.affiliation: Department of Experimental Medicine, Institute of Cardiology of Rio Grande do Sul, University Foundation of Cardiology, Porto Alegre, Brazil. editoracao-pc@cardiologia.org.br
authors.forename: Beatriz D'Agord
authors.initials: BD
authors.lastname: Schaan
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Marcello C
authors.initials: MC
authors.lastname: Bertoluci
authors.forename: Nelson Gianni de
authors.initials: NG
authors.lastname: Lima
authors.forename: Juliana
authors.initials: J
authors.lastname: Passaglia
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hermes
authors.forename: Fabio Ramos
authors.initials: FR
authors.lastname: Oliveira
authors.forename: Maristela
authors.initials: M
authors.lastname: Okamoto
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D007672:Kidney Cortex; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013311:Streptozocin; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; C495679:Slc2a1 protein, rat; C495683:Slc2a2 protein, rat; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013311:Streptozocin