Increased renal GLUT1 abundance and urinary TGF-beta 1 in streptozotocin-induced diabetic rats: implications for the development of nephropathy complicating diabetes.
Increased expression of transforming growth factor beta-1 (TGF-beta 1) and glucose transporter (GLUT1) has been implicated in the genesis of diabetic nephropathy. The aim of this study was to evaluate GLUT1 protein levels in the renal cortex of a rat model of diabetes as well as its relationship to urinary albumin and TGF-beta1. Streptozotocin-injected rats (n = 13) and controls (n = 13) were compared for their urinary albumin, and TGF-beta 1 and for renal cortical and medullar GLUT1 protein abundance. GLUT1 protein content was determined by optical densitometry after Western blotting using an anti-GLUT1 antibody; urinary albumin was measured using electroimmunoassay, urinary TGF-beta 1 using ELISA. Forty-five days of diabetes resulted in increased albuminuria (p < 0.05), urinary TGF-beta 1 (p < 0.05) and GLUT1 protein abundance (p < 0.05). There was a positive correlation between urinary TGF-beta 1 and plasma glucose levels (r = 0.65, p < 0.05) and albuminuria (r = 0.72, p < 0.05). We concluded that 45 days of diabetes result in incipient diabetic nephropathy and increased cortical GLUT1 protein abundance. We speculate that the higher cortical GLUT1 protein levels in diabetes may amplify the effects of hyperglycemia in determining higher intracellular glucose in mesangial cells, thereby contributing to diabetes-related kidney damage.
D'Agord Schaan
B
B
Curso de Pós-Graduação, Clínica Médica, Departamento de Fisiologia, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Universidade de São Paulo, Brazil.
Lacchini
S
S
Bertoluci
M C
MC
Irigoyen
M C
MC
Machado
U F
UF
Schmid
H
H
D000419:Albuminuria / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000652:urine; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000652:urine; D051272:Glucose Transporter Type 1; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000652:urine*
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D016212:Transforming Growth Factor beta