Inhibition of vascular endothelial growth factor (VEGF) does not affect early renal changes in a rat model of lean type 2 diabetes

Horm Metab Res. 2005 Jan;37(1):21-5. doi: 10.1055/s-2005-861027.

Abstract

Type 2 diabetes is the most frequent cause of end-stage renal failure in many Western countries. Approximately 10-15 % of all type 2 diabetics are lean. Various growth factors and cytokines have been implicated in the pathophysiology of diabetic kidney disease, including vascular endothelial growth factor (VEGF). To elucidate a role for VEGF in the renal changes associated with type 2 diabetes, we examined the effect of a VEGF-antibody (ab) on early renal changes in the Goto-Kakizaki (GK) rat, a lean type 2 diabetes model. GK-rats were treated for 6 weeks with the VEGF-ab or with an isotype-matched irrelevant IgG. Wistar rats were used as non-diabetic controls. Placebo-treated GK-rats showed a pronounced increase in glomerular volume and urinary albumin excretion (UAE) and no change in the renal expression of endothelial nitric oxide synthase (eNOS) compared to placebo-treated non-diabetic controls. Kidney weight and creatinine clearance were no different between the groups. VEGF-ab treatment had no effect on glomerular volume, UAE, eNOS expression, body weight, blood glucose levels or food intake, but lowered serum insulin levels in non-diabetic and diabetic animals. We conclude that VEGF inhibition has minimal effects on early renal changes in GK-rats.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / complications
  • Albuminuria / enzymology
  • Animals
  • Blood Glucose / metabolism
  • Body Composition
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / physiopathology*
  • Disease Models, Animal
  • Female
  • Kidney / pathology
  • Kidney Glomerulus / enzymology
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology*
  • Liver / pathology
  • Myocardium / pathology
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Organ Size
  • Random Allocation
  • Rats
  • Rats, Inbred Strains
  • Rats, Wistar
  • Thinness / physiopathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Blood Glucose
  • Vascular Endothelial Growth Factor A
  • Creatinine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat