NDT Advance Access originally published online on May 23, 2006
Nephrology Dialysis Transplantation 2006 21(9):2399-2405; doi:10.1093/ndt/gfl212
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
PPAR-
and -
agonists attenuate diabetic kidney disease in the apolipoprotein E knockout mouse
1 JDRF Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute2 Department of Medicine, Monash University, Melbourne, Australia
Correspondence and offprint requests to: Anna C Calkin, JDRF/Danielle Alberti Memorial Centre for Diabetes complications, Baker Heart Research Institute, PO Box 6492, St Kilda Rd Central, Melbourne 8008, Australia. Email: anna.calkin{at}baker.edu.au
Backgound. Peroxisome proliferator-activated receptor (PPAR)-
and PPAR-
agonists are widely used in diabetes. In addition to their effects on lipid and glucose homeostasis, these agents have been postulated to have independent renoprotective actions. In the current study, we assess the efficacy of the PPAR- agonist, gemfibrozil, the PPAR- agonist rosiglitazone and the non-thiazolidinedione PPAR-/ coagonist, compound 3q, on kidney structure and function in streptozotocin-treated apolipoprotein E knockout mice.
Methods. Control and streptozotocin-diabetic mice were randomized to receive rosiglitazone (20 mg/kg/day), gemfibrozil (100 mg/kg/day), or compound 3q (3 mg/kg/day) by gavage, or no treatment for a period of 20 weeks. Renal fibrosis was assessed by standard histology and collagen IV immunohistochemistry. Kidney function was assessed by urinary albumin excretion and creatinine clearance.
Results. Diabetes in this model was associated with an increase in glomerulosclerosis, tubulointerstitial fibrosis and increased collagen IV deposition in the glomeruli and tubules. All three agents significantly attenuated glomerulosclerosis, tubulointerstitial expansion and collagen IV deposition. The increase in albuminuria and the decline in kidney function associated with diabetes in this model were also attenuated by each of these agents, with no superiority observed among various treatment groups. These renoprotective effects were observed in the absence of changes in glucose, insulin or lipid levels or a reduction in blood pressure.
Conclusions. Combined with their independent anti-atherosclerotic actions, and their important effects on dyslipidaemia and insulin resistance, PPAR agonists may be useful for the prevention of diabetic complications, including kidney disease, even in type 1 diabetes.
Keywords: diabetes; diabetic kidney disease; glomerulosclerosis; insulin-dependent diabetes mellitus; peroxisome proliferator-activated receptor; tubulointerstitial fibrosis
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Wang, W. Feng, W. Xue, Y. Tan, D. W. Hein, X.-K. Li, and L. Cai Inactivation of GSK-3{beta} by Metallothionein Prevents Diabetes-Related Changes in Cardiac Energy Metabolism, Inflammation, Nitrosative Damage, and Remodeling Diabetes, June 1, 2009; 58(6): 1391 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kono, Y. Kamijo, K. Hora, K. Takahashi, M. Higuchi, K. Kiyosawa, H. Shigematsu, F. J. Gonzalez, and T. Aoyama PPAR{alpha} attenuates the proinflammatory response in activated mesangial cells Am J Physiol Renal Physiol, February 1, 2009; 296(2): F328 - F336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Sen, W. E. Rodriguez, N. Tyagi, M. Kumar, S. Kundu, and S. C. Tyagi Ciglitazone, a PPAR{gamma} agonist, ameliorates diabetic nephropathy in part through homocysteine clearance Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1205 - E1212. [Abstract] [Full Text] [PDF]
|
|