A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse.
BACKGROUND
PTR-3173 (S) is a novel somatostatin analogue that has been found to exert a prolonged inhibitory action on the growth hormone (GH)-insulin-like growth factor (IGF)-I axis, but not on insulin secretion. We investigated the potential effect of this agent on the development of markers of diabetic nephropathy in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes.


METHODS
Female diabetic NOD mice treated with PTR-3173 (DS group) or saline (D) and their control groups of nonhyperglycemic age-matched littermates (C) and C mice treated with PTR-3173 (CS) were sacrificed three weeks after onset of diabetes.


RESULTS
Serum GH was elevated in the D group, decreased in the DS group, and unchanged in the CS group. Serum IGF-I was significantly decreased in both the D and DS groups. Kidney weight, glomerular volume, albuminuria, and creatinine clearance were increased in the D animals and showed a trend toward normalization in the DS animals. Renal extractable IGF-I protein and IGFBP1 mRNA were increased in the D group and normalized in the DS group.


CONCLUSIONS
GH antagonism by PTR-3173 has a blunting effect on renal/glomerular hypertrophy, albuminuria, and glomerular filtration rate (GFR) in diabetic NOD mice. This phenomenon is apparently associated with the prevention of renal IGF-I accumulation. Thus, modulation of GH effects may have beneficial therapeutic implications in diabetic nephropathy.
Landau
D
D
Department of Pediatrics, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel. ldaniel@bgumail.bgu.ac.il
Segev
Y
Y
Afargan
M
M
Silbergeld
A
A
Katchko
L
L
Podshyvalov
A
A
Phillip
M
M
D000419:Albuminuria / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000097:blood; D006984:Hypertrophy; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; C420459:PTR 3173; D012333:RNA, Messenger; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003404:Creatinine