Troglitazone has been shown to improve peripheral
insulin resistance in type 2 diabetic patients and animal models. We examined the effect of
troglitazone on the expression of
glucose transporter 4 (GLUT4) in muscle and adipose tissue from Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of obese
type 2 diabetes mellitus. In addition, the effects of
troglitazone on GLUT4 translocation and on
glucose transport activity in adipocytes were also evaluated. Muscle and adipose tissues were isolated from 35-week-old male
troglitazone-treated and untreated OLETF rats at a dose of 150 mg/kg per day for 14 days. In skeletal muscle, the
protein and
mRNA levels of GLUT4 were not significantly different between OLETF and control rats and they were not affected by
troglitazone. On the other hand,
GLUT4 protein and
mRNA levels in adipose tissue from OLETF rats were significantly decreased (P<0.01) compared with control rats and they were significantly increased (1.5-fold, P<0.01) by
troglitazone.
Troglitazone had no major effect on GLUT4 translocation in adipocytes, but it significantly increased (1.4-fold, P<0.05) the basal and
insulin-induced amounts of GLUT4 in plasma membrane (PM) in adipocytes from OLETF rats. Consistent with these results, the basal and
insulin-induced
glucose uptakes in adipocytes from
troglitazone-treated OLETF rats were significantly increased (1.5-fold, P<0.05) compared with untreated OLETF rats. Our results suggest that
troglitazone may exert beneficial effects on
insulin resistance by increasing the expression of GLUT4 in adipose tissue.