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


CONCLUSIONS
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.
Segev
Yael
Y
Department of Micrbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Eshet
Renanah
R
Rivkis
Inessa
I
Hayat
Chen
C
Kachko
Leonid
L
Phillip
Moshe
M
Landau
Daniel
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D024141:Collagen Type IV; C420459:PTR 3173; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone