TY - JOUR
T1 - The effect of growth hormone on the development of diabetic kidney disease in rats
AU - Landau, Daniel
AU - Israel, Eytan
AU - Rivkis, Inessa
AU - Kachko, Leonid
AU - Schrijvers, Bieke F.
AU - Flyvbjerg, Allan
AU - Phillip, Moshe
AU - Segev, Yael
N1 - Funding Information:
Acknowledgements. We thank Dr M. Frieger, from the Department of Epidemiology, Faculty of Health Sciences, Ben Gurion University, for the statistical evaluation of data. We also thank Chen Chayat, for the excellent technical assistance. This study was partially funded by a grant from the American Physicians Fellowship for Medicine in Israel.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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), nondiabetic 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 hyper-filtration 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.
AB - 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), nondiabetic 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 hyper-filtration 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.
KW - Diabetes insulin-dependent
KW - Insulin-like growth factor
KW - Insulin-like growth factor binding protein-1
KW - Somatotropin
KW - Steptozotocin
UR - http://www.scopus.com/inward/record.url?scp=0037383768&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfg142
DO - 10.1093/ndt/gfg142
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C2 - 12637637
AN - SCOPUS:0037383768
SN - 0931-0509
VL - 18
SP - 694
EP - 702
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 4
ER -
