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 fou nd to exert a prolonged inhibitory action on the growth hormone (GH)-insuli n-like growth factor (IGF)-I axis, but not on insulin secretion. We investi gated the potential effect of this agent on the development of markers of d iabetic nephropathy in the nonobese diabetic (NOD) mouse model of insulin-d ependent diabetes. Methods. Female diabetic NOD mice treated with PTR-3173 (DS group) or salin e (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, a nd unchanged in the CS group. Serum IGF-I was significantly decreased in bo th the D and DS groups. Kidney weight, glomerular volume, albuminuria, and creatinine clearance were increased in the D animals and showed a trend tow ard normalization in the DS animals. Renal extractable IGF-I protein and IG FBP1 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/glome rular hypertrophy. albuminuria, and glomerular filtration rate (GFR) in dia betic NOD mice. This phenomenon is apparently associated with the preventio n of renal IGF-I accumulation. Thus. modulation of GH effects may have bene ficial therapeutic implications in diabetic nephropathy.