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J Biol Chem, Vol. 273, Issue 9, 5315-5322, February 27, 1998
From the Various biological responses stimulated by
insulin have been thought to be regulated by phosphatidylinositol
3-kinase, including glucose transport, glycogen synthesis, and protein
synthesis. However, the molecular link between phosphatidylinositol
3-kinase and these biological responses has been poorly understood.
Recently, it has been shown that protein kinase B (PKB/c-Akt/Rac) lies
immediately downstream from phosphatidylinositol 3-kinase. Here, we
show that expression of a constitutively active form of PKB induced
glucose uptake, 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 rapamycin-sensitive serine/threonine kinase by PKB in L6 myotubes
might be involved in the enhancement of glycogen synthesis and protein
synthesis, respectively. These results suggest that PKB acts as a key
enzyme linking phosphatidylinositol 3-kinase activation to multiple
biological functions of insulin through regulation of downstream
kinases in skeletal muscle, a major target tissue of insulin.
Potential Role of Protein Kinase B in Insulin-induced Glucose
Transport, Glycogen Synthesis, and Protein Synthesis
§,,,,,
,,, and
Third Department of Internal Medicine,
Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo
113, Japan, § The Institute for Diabetes Care and Research,
Asahi Life Foundation, 1-6-6 Marunouchi, Chiyoda-ku, Tokyo 100, Japan,
¶ Laboratory for Physiological Chemistry, Utrecht
University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands, and
Department of Pulmonary Disease, University Hospital Utrecht,
Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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