Clostridium botulinum C3 exoenzyme stimulates GLUT4-mediated glucose transport, but not glycogen synthesis, in 3T3-L1 adipocytes--a potential role of rho?
The signal transduction pathway by which insulin stimulates glucose transport is largely unknown, but a role of PI-3-kinase and small GTP-binding proteins has been proposed. In previous studies we, among many others, excluded a role for the ras/MAP kinase pathway in insulin-mediated glucose transport. In this study we examined a possible role of the small GTP-binding protein rho in this process. Pretreatment of 3T3-L1 adipocytes with botulinum C3 exoenzyme (C3), which is known to ADP-ribosylate and inactivate rho, potently stimulated glucose uptake to a level similar to insulin. Interestingly, glycogen synthesis was not affected by C3 treatment. Insulin stimulates glucose uptake by triggering the translocation of GLUT4, the insulin-sensitive glucose transporter isotype, from an intracellular compartment to the plasma membrane. Similarly, C3-induced glucose uptake was paralleled by GLUT4 translocation. These data point to an important and novel role of the target of C3 (likely rho) in the regulation of GLUT4-mediated glucose transport. Our data suggest that insulin might stimulate glucose uptake through inactivation of rho.
van den Berghe
N
N
Department of Endocrinology, University Hospital Leiden, The Netherlands. van-den-berghe@mpi-dortmund.mpg.de
Barros
L F
LF
van Mackelenbergh
M G
MG
Krans
H M
HM
D016475:3T3 Cells; D036002:ADP Ribose Transferases / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001905:Botulinum Toxins; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000096:biosynthesis*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D013379:Substrate Specificity
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D006003:Glycogen; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D001905:Botulinum Toxins; D005947:Glucose