Effect of metformin treatment on insulin action in diabetic rats: in vivo and in vitro correlations.

Abstract The mechanism (both at the whole body and cellular level) by which metformin improves insulin sensitivity has yet to be defined. In the present study, we examined in vivo insulin-mediated whole-body glucose disposal, glycogen synthesis, hepatic glucose production, and insulin secretion, as well as in vitro muscle insulin receptor tyrosine kinase activity in eight control, eight neonatal streptozotocin diabetic rats, and eight diabetic rats before and after treatment with metformin. Ten weeks after birth diabetic rats had higher fasting (132 + 5 v 101 + 2 mg/dL) and postmeal (231 + 10 v 133 + 3) plasma glucose levels compared with controls ( P P v 18.3 + 1.0 mg/kg · min) insulin clamp study and was increased to values greater ( P 3 H-3-glucose radioactivity, was diminished by 25% ( P r = .82, P max ) (32 v 45 pmol/mg · min, P P r = .82, P r = .64, P