Amelioration of insulin resistance but not hyperinsulinemia in obese mice overexpressing GLUT4 selectively in skeletal muscle

The effects of gold-thioglucose (GTG) treatment were examined in mice overe xpressing GLUT4 selectively in skeletal muscle (MLC-GLUT4 mice) and in age- matched controls. Groups of MLC-GLUT4 and control mice were injected with G TG or saline at 5 weeks of age. At 12 weeks following the injections, GTG-t reated control mice exhibited a 35% increase in body weight versus saline-t reated controls. Similarly, a 30% increase in body weight was observed in G TG-treated MLC-GLUT4 mice compared with saline-treated MLC-GLUT4 mice 12 we eks after the injections. In saline-treated lean MLC-GLUT4 and control mice , intraperitoneal injection of insulin decreased blood glucose in 1 hour by 63% and 38%, respectively. Insulin also decreased blood glucose by 40% in GTG-treated obese MLG-GLUT4 mice after 1 hour. However, insulin did not red uce blood glucose levels in GTG-treated obese control mice. The ability of insulin to clear blood glucose in GTG-treated obese MLC-GLUT4 mice is assoc iated with increased skeletal muscle GLUT4 content and white adipose tissue (WAT) GLUT4 content as compared with GTG-treated obese controls. However, fasting blood glucose levels in GTG-treated obese MLC-GLUT4 and control mic e were elevated by approximately 30% compared with saline-treated groups. L astly, although GTG-treated obese MLC-GLUT4 mice exhibited improved glucose clearance in response to insulin, they nevertheless remained as hyperinsul inemic as GTG-treated obese control mice. These results suggest that geneti c overexpression of GLUT4 in skeletal muscle may ameliorate the development of insulin resistance associated with obesity but cannot restore normal gl ucose and insulin levels. Copyright (C) 2000 by W.B. Saunders Company.