Inhibition of vascular endothelial growth factor (VEGF) does not affect early renal changes in a rat model of lean type 2 diabetes.
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.
Schrijvers
B F
BF
Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark. Bieke.Schrijvers@UGent.be
De Vriese
A S
AS
Tilton
R G
RG
Van de Voorde
J
J
Denner
L
L
Lameire
N H
NH
Flyvbjerg
A
A
D000419:Albuminuria / Q000150:complications / Q000201:enzymology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013851:Thinness / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001786:Blood Glucose; D042461:Vascular Endothelial Growth Factor A; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat