The effect of growth hormone on the development of diabetic kidney disease in rats.
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.
Landau
Daniel
D
Department of Pediatrics, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel. ldaniel@bgumail.bgu.ac.il
Israel
Eytan
E
Rivkis
Inessa
I
Kachko
Leonid
L
Schrijvers
Bieke F
BF
Flyvbjerg
Allan
A
Phillip
Moshe
M
Segev
Yael
Y
D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001707:Biopsy, Needle; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000473:pathology*; D004195:Disease Models, Animal; D013006:Growth Hormone / Q000494:pharmacology*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000032:analysis; D012016:Reference Values; D018709:Statistics, Nonparametric; D013311:Streptozocin; D016482:Urinalysis
D012333:RNA, Messenger; D013311:Streptozocin; D013006:Growth Hormone; D017526:Receptor, IGF Type 1