M. Emoto et al., Troglitazone treatment increases plasma vascular endothelial growth factorin diabetic patients and its mRNA in 3T3-L1 adipocytes, DIABETES, 50(5), 2001, pp. 1166-1170
Troglitazone is one of the thiazolidinediones, a new class of oral antidiab
etic compounds that are ligands of peroxisome proliferator-activated recept
or-gamma. This study on vascular endothelial growth factor (VEGF), also kno
wn as vascular permeability factor, was prompted by our clinical observatio
n that the characteristics of troglitazone-induced edema were very similar
to those caused by vascular hyperpermeability. when Japanese diabetic patie
nts mere screened for plasma VEGF, me found levels to be significantly (P <
0.001) increased in troglitazone-treated subjects (120.1 +/- 135.0 pg/ml,
n = 30) compared with those treated with diet alone (29.2 +/- 36.1 pg/ml, n
= 10), sulfonylurea (25.8 +/- 22.2 pg/ml, n = 10), or insulin (24.6 +/- 19
.0 pg/ml, n = 10). Involvement of troglitazone in increased VEGF levels was
further supported by the plasma VEGF levels in five patients before treatm
ent (20.2 +/- 7.0 pg/ml), after 3 months of troglitazone treatment (83.6 +/
- 65.9 pg/ml), and 3 months after discontinuation (28.0 +/- 11.6 pg/ml). we
further demonstrated that troglitazone, as well as rosiglitazone, at the p
lasma concentrations observed in patients, increased VEGF mRNA levels in 3T
3-L1 adipocytes. VEGF is an angiogenic and mitogenic factor and is currentl
y considered the most likely cause of neovascularization and hyperpermeabil
ity in diabetic proliferative retinopathy. Although increased VEGF may be b
eneficial for subjects with macroangiopathy and troglitazone is currently n
ot available for clinical use, vascular complications, especially diabetic
retinopathy, must be followed with great caution in subjects treated with t
hiazolidinediones.