Effect of pioglitazone on diabetic nephropathy and expression of HIF-1α and VEGF in the renal tissues of type 2 diabetic rats

Diabetes Res Clin Pract. 2011 Jul;93(1):63-9. doi: 10.1016/j.diabres.2011.03.019. Epub 2011 Apr 22.

Abstract

Objective: To investigate the effect of pioglitazone on the progression of diabetic nephropathy and the expression of hypoxia inducible factor-1α (HIF-1a) and vascular endothelial growth factor (VEGF) in a rat model of type-2 diabetes.

Methods: Streptozotocin-induced type-2 diabetes mellitus (DM) model was set up in male Sprague Dawley rats. DM rats were treated with or without pioglitazone (4 mg/kg/day for 8 weeks) and/or cobalt chloride. Normal rats were used as controls. The blood chemistry, urine albumin, kidney histology, and expression of HIF-1α and VEGF of the different groups were compared.

Results: The kidney weights and kidney weight indexes of DM rats were significantly higher than in NC rats (P<0.01) and the kidney weights and kidney weight indexes of rats in pioglitazone and/or cobalt chloride treatment group were significantly less than in DM group. Relative to rats in the NC group, rats in the DM group had significantly disrupted serum chemistry, urinary albumin, and kidney histology, and significantly enhanced expression of HIF-1a and VEGF. Rats in the pioglitazone and/or cobalt chloride treatment group experienced significant amelioration of these effects.

Conclusion: In a rat model, pioglitazone ameliorated many of the physiological, cellular, and molecular processes associated with diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunohistochemistry
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Organ Size / drug effects
  • Pioglitazone
  • Rats
  • Rats, Sprague-Dawley
  • Thiazolidinediones / therapeutic use*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Thiazolidinediones
  • Vascular Endothelial Growth Factor A
  • Pioglitazone