Phosphatidylinositol 3-Kinase Redistribution Is Associated With Skeletal Muscle Insulin Resistance in

Insulin resistance during pregnancy provokes gesta-tional diabetes mellitus (GDM); however, the cellular mechanisms for this type of insulin resistance are not well understood. We evaluated the mechanisms(s) for insulin resistance in skeletal muscle from an animal model of spontaneous GDM, the heterozygous C57BL/ KsJ-db/ mouse. Pregnancy triggered a novel functional redistribution of the insulin-signaling environment in skeletal muscle in vivo. This environment preferentially increases a pool of phosphatidylinositol (PI) 3-kinase activity associated with the insulin receptor, away from insulin receptor substrate (IRS)-1. In conjunction with the redistribution of PI 3-kinase to the insulin receptor, there is a selective increase in activation of downstream serine kinases Akt and p70S6. Furthermore, we sho