Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation.
Akt is a serine/threonine kinase that requires a functional phosphatidylinositol 3-kinase to be stimulated by insulin and other growth factors. When directed to membranes by the addition of a src myristoylation sequence, Akt becomes constitutively active. In the present studies, the constitutively active Akt and a nonmyristoylated control mutant were expressed in 3T3-L1 cells that can be induced to differentiate into adipocytes. The constitutively active Akt induced glucose uptake into adipocytes in the absence of insulin by stimulating translocation of the insulin-responsive glucose transporter 4 to the plasma membrane. The constitutively active Akt also increased the synthesis of the ubiquitously expressed glucose transporter 1. The increased glucose influx in the 3T3-L1 adipocytes directed lipid but not glycogen synthesis. These results indicate that Akt can regulate glucose uptake and metabolism.
Kohn
A D
AD
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA. roth@cmgm.stanford.edu
Summers
S A
SA
Birnbaum
M J
MJ
Roth
R A
RA
D016475:3T3 Cells; D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000096:biosynthesis; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D008055:Lipids; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009227:Myristic Acids; D011518:Proto-Oncogene Proteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D019814:Myristic Acid; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose