Potential Role of Protein Kinase B in Insulin-induced Glucose Transport, Glycogen Synthesis, and Protein Synthesis

Various biological responses stimulated by insulin have been thought to be regulated by phosphatidylinosi-tol 3-kinase, including glucose transport, glycogen syn-thesis, and protein synthesis. However, the molecular link between phosphatidylinositol 3-kinase and these biological responses has been poorly understood. Re-cently, it has been shown that protein kinase B (PKB/c-Akt/ Rac) lies immediately downstream from phosphati-dylinositol 3-kinase. Here, we show that expression of a constitutively active form of PKB induced glucose up-take, glycogen synthesis, and protein synthesis in L6 myotubes downstream of phosphatidylinositol 3-kinase and independent of Ras and mitogen-activated protein kinase activation. Introduction of constitutively active PKB induced glucose uptake and protein synthesis but not glycogen synthesis in 3T3L-1 adipocytes, which lack expression of glycogen synthase kinase 3 different from L6 myotubes. Furthermore, we show that deactivation of glycogen synthase kinase 3 and activation of rapamy-cin- sensitive serine/threonine kinase by PKB in L6 myo-tubes might be involved in the enhancement of glycogen synthesis and protein synthesis, respectively. These re-sults suggest that PKB acts as a key enzyme linking phosphatidylinositol 3-kinase activation to multiple bi-ological functions of insulin through regulation of downstream kinases in skeletal muscle, a major target tissue of insulin