PPARgamma agonists diminish serum VEGF elevation in diet-induced insulin resistant SD rats and ZDF rats.
We investigated the effect of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists on serum vascular endothelial growth factor (VEGF) in diet-induced insulin resistant SD rats and ZDF rats. SD rats fed a high fat/sucrose diet showed increases in serum insulin and VEGF (both p < 0.01). Treatment with a PPARgamma agonist GI262570 normalized the diet-elevated insulin and VEGF (both p < 0.01). There was a positive correlation between serum insulin and VEGF (p < 0.05) in SD rats. ZDF rats had higher serum glucose, insulin, and VEGF than Zucker lean rats (all p < 0.01). Treatment of ZDF rats with PPARgamma agonist pioglitazone decreased serum glucose and VEGF (both p <0.01). There was a positive correlation between glucose and VEGF in ZDF rats (p < 0.05). In 3T3-L1 adipocytes, GI262570 did not affect insulin-stimulated VEGF secretion. These studies demonstrated that hyperinsulinemia in SD rats and hyperglycemia in ZDF rats were associated with increased serum VEGF; PPARgamma agonists normalized serum insulin, glucose, and VEGF, but did not affect VEGF secretion in vitro.
Department of Molecular Pharmacology, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. baichun.w.yang@gsk.com
Baichun
B
Yang
Peiyuan
P
Lin
Kevin M
KM
Carrick
Judi A
JA
McNulty
Lisa G
LG
Clifton
Deborah A
DA
Winegar
Jay C
JC
Strum
Stephen A
SA
Stimpson
Greg L
GL
Pahel
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000008:administration & dosage*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D007328:Insulin; D010080:Oxazoles; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A; C422415:farglitazar; D014443:Tyrosine