A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse

Daniel Landau, Yael Segev, Michel Afargan, Aviva Silbergeld, Leonid Katchko, Andrey Podshyvalov, Moshe Phillip

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)505-512
Number of pages8
JournalKidney International
Volume60
Issue number2
DOIs
StatePublished - 1 Jan 2001

Keywords

  • Albuminuria
  • Diabetes
  • Growth hormone
  • Insulin-like growth factor-I
  • PTR-3173
  • Renal hypertrophy

Fingerprint

Dive into the research topics of 'A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse'. Together they form a unique fingerprint.

Cite this