Nephrol Dial Transplant (2003) 18: 694-702
© 2003 European Renal Association-European Dialysis and Transplant Association
The effect of growth hormone on the development of diabetic kidney disease in rats
1 Department of Pediatrics, 2 Department of Immunology and 3 Department of Pathology, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel, 4 Medical Department M, Medical Research Laboratory M, Institute of Experimental Clinical Research, Aarhus Kommunehospital, Aarhus C, Denmark and 5 Felsenstein Medical Research Center, Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Background. Nephropathy is the most severe complication of diabetes mellitus. We investigated the effect of exogenous growth hormone (GH) administration on renal function and matrix deposition in the streptozotocin (STZ) model of type I-diabetic rat.
Methods. Adult female STZ-diabetic rats (D), non-diabetic control rats injected with saline (C) and control and diabetic rats injected with bovine GH for 3 months (CGH and DGH, respectively) were used.
Results. The usual renal hypertrophy seen in D animals was more pronounced in the DGH group. Creatinine clearance increased only in the D rats, but not in the other groups, including DGH. Albuminuria was observed in the D animals but was significantly elevated in the DGH group. Glomeruli from DGH animals showed more extensive matrix accumulation (manifested as an increase in mesangial/glomerular area ratio). Renal extractable insulin-like growth factor (IGF-I) mRNA was decreased in the D and DGH groups, but renal IGF-I protein was not significantly increased. Renal IGF binding protein-1 was increased in the D groups and further increased in the DGH group, at both the mRNA and protein levels.
Conclusions. GH-treated diabetic rats had less hyperfiltration and more albuminuria, concomitant with more glomerular matrix deposition, when compared with regular diabetic animals. This was associated with a significant increase in renal IGFBP-1, and dissociated from IGF-I changes. Thus, in this model, GH exacerbates the course of diabetic kidney disease.
Keywords: diabetes insulin-dependent; insulin-like growth factor; insulin-like growth factor binding protein-1; somatotropin; steptozotocin
Correspondence and offprint requests to: Daniel Landau, MD, Pediatric Nephrology, Department of Pediatrics, Soroka Medical Center, P.O. Box 151, Beer Sheva 84101, Israel. Email: ldaniel{at}bgumail.bgu.ac.il
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