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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.

We investigated the intrarenal distribution of transforming growth factor-beta 1 (TGF-beta 1) protein and the TGF-beta 1 mRNA levels in the glomeruli and renal cortex of Wistar rats with streptozotocin-induced diabetes before and after the onset of diabetic nephropathy. Monthly urinary albumin excretion, glomerular filtration rate, glomerular volume, renal histology and immunohistochemical reaction for type-I collagen were also studied. The results showed progressively higher glomerular immunohistochemical TGF-beta 1 staining in rats with a diabetes duration of 24 and 40 weeks which was correlated with albuminuria (r = 0.905, p < 0.01) and was temporally associated with the appearance of glomerular deposition of total and type-I collagen. The glomerular content of TGF-beta 1 mRNA was higher in rats diabetic for 20 weeks while lower cortical RNA-TGF-beta 1 levels were found in rats with a diabetes duration of 1-40 weeks. These data suggest that this polypeptide may be an important mediator of diabetic glomerulosclerosis.