Plasma Membrane Content of Glucose Transporter 4 in Skeletal Muscle and Visceral Fat in OLETF Rats Treated with Troglitazone.

Abstract

The exact mechanism by which troglitazone improves insulin sensitivity is not well understood. Eight 35-week-old male diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with troglitazone (30mg/kg body weight/d) for 20d (OLETF-T). Body composition, glucose tolerance, serum lipid profile and expression of glucose transporter 4 (Glut 4) in OLETF-T were compared with those in 8 male control OLETF rats and in 18 normal Long Evans Tokushima Otsuka (LETO) rats. Body weight, visceral fat weight, and pancreas weight in OLETF-T rats were significantly lower than those in OLETF rats (p<0.05). Furthermore, troglitazone treatment attenuated atrophy and fibrosis of the pancreas. Serum concentrations of glucose, triglyceride, total cholesterol and immunoreactive insulin (IRI) were also significantly lower in OLETF-T rats. Expression of Glut 4 in plasma membrane fractions of skeletal muscle and viscera fat was detected by Western blot. The amount of Glut 4 protein in skeletal muscle in OLETF rats was 52% of that in LETO rats, and 75% for OLETF-T rats. In visceral fat, Glut 4 expressions in OLETF and OLETF-T rats were 38% and 83%, respectively, of that in LETO rats. Thus, treatment with troglitazone prevented the decrease of Glut 4 expression seen in OLETF rats. Glucose tolerance was improved significantly by the treatment, and the amount of secreted IRI in response to oral glucose tolerance test was 1798pM, 702.2pM, and 1103.5pM, in OLETF, OLETF-T and LETO rats, respectively. The data presented suggest that treatment with troglitazone increased the Glut 4 expression in both skeletal and visceral fat tissues of OLETF rats, which may result in the improvement of insulin sensitivity and preservation of pancreas function.