ptr-3173 and Hypertrophy

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.. 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.. 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.. 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.

Topics: Albuminuria; Animals; Blood Glucose; Blotting, Northern; Creatinine; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Growth Hormone; Hypertrophy; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Kidney Glomerulus; Mice; Mice, Inbred NOD; Organ Size; RNA, Messenger; Somatostatin