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Horm Metab Res 2005; 37(1): 21-25
DOI: 10.1055/s-2005-861027
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of Vascular Endothelial Growth Factor (VEGF) Does Not Affect Early Renal Changes in a Rat Model of Lean Type 2 Diabetes

B.  F.  Schrijvers1, 2 , A.  S.  De Vriese2, 3 , R.  G.  Tilton4 , J.  Van De Voorde5 , L.  Denner4 , N.  H.  Lameire2 , A.  Flyvbjerg1
  • 1Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark
  • 2Renal Unit, Department of Internal Medicine, Gent University Hospital, Gent, Belgium
  • 3Renal Unit, Department of Internal Medicine, AZ Sint-Jan AV, Brugge, Belgium
  • 4Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
  • 5Department of Physiology and Physiopathology, Gent University, Gent, Belgium
Further Information

Publication History

Received 15 April 2004

Accepted after second Revision 20 July 2004

Publication Date:
09 February 2005 (online)

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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.

Key words

Endothelial nitric oxide synthase (eNOS) - Glomerular volume - Goto-Kakizaki (GK) rat - Kidney growth - VEGF-antibody (ab)

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Bieke Schrijvers, M. D.

Renal Unit, 0K12A, Gent University Hospital

De Pintelaan 185 · 9000 Gent · Belgium

Phone: +32 (9) 2403365

Fax: +32 (9) 2403059

Email: Bieke.Schrijvers@UGent.be