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NDT Advance Access published online on October 19, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh528
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received August 27, 2003
Accepted September 7, 2004

Original Articles

Comparison between somatostatin analogues and ACE inhibitor in the NOD mouse model of diabetic kidney disease

Yael Segev 1, Renanah Eshet 1, Inessa Rivkis 1, Chen Hayat 1, Leonid Kachko 2, Moshe Phillip 3, and Daniel Landau 4*

1 Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
2 Department of Pathology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
3 Felsenstein Medical Research Center, Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach Tikva, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
4 Department of Pediatrics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

* To whom correspondence should be addressed.
Daniel Landau, E-mail: ldaniel{at}bgumail.bgu.ac.il



  Abstract

Background. The growth hormone (GH)-insulin-like growth factor (IGF)-SST (SST) axis is involved in diabetic nephropathy (DN). We have recently shown a beneficial effect on diabetic kidney disease markers by the use of a novel somatostatin (SST) analogue (PTR-3173) (S). The purpose of this study is to compare the effects of S with a previously used SST analogue (octreotide) and an ACE inhibitor (ACEi), a standard of care in DN.

Methods. Non-obese diabetic mice (a model of type I diabetes) were treated with either S (DS), octreotide (DO), enalapril (DA), or PTR-3173 and enalapril (DAS group) for 3 weeks.

Results. Diabetic renal hypertrophy was blunted in the DS and DO groups only. Serum GH and IGF-I were markedly increased and decreased, respectively, in the D group, a change significantly blunted in DO and DS. Diabetic hyperfitration and albuminuria were blunted in all the four treated diabetic groups. The marked deposition of type IV collagen and PAS material were mildly decreased in DA, but more markedly reduced in DS as well as DO. Diabetic renal laminin accumulation was suppressed in all treated animal groups. No synergistic effect was observed for any parameter in the combination group DAS.

Conclusion. SST analogues exert beneficial effects in most parameters of diabetic kidney disease to the same extent as the ACEi. Enalapril treatment had no effect on renal hypertrophy and did not cause a significant decrease in mesangial type IV collagen deposition. A synergistic effect of combined SST-ACEi therapy could not be shown in this study.

Keywords: diabetic nephropathies; growth hormone; insulin-like growth factor I; immunohistochemistry.
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