Clostridium botulinum C3 exoenzyme stimulates GLUT4-mediated glucose transport, but not glycogen synthesis, in 3T3-L1 adipocytes--a potential role of rho?

Biochem Biophys Res Commun. 1996 Dec 13;229(2):430-9. doi: 10.1006/bbrc.1996.1821.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • ADP Ribose Transferases / metabolism*
  • Adipocytes / metabolism*
  • Animals
  • Biological Transport
  • Botulinum Toxins*
  • Enzyme Activation
  • Glucose / metabolism*
  • Glucose Transporter Type 4
  • Glycogen / biosynthesis*
  • Insulin / metabolism
  • Mice
  • Microscopy, Confocal
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins*
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Substrate Specificity


  • Glucose Transporter Type 4
  • Insulin
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Slc2a4 protein, mouse
  • Glycogen
  • ADP Ribose Transferases
  • exoenzyme C3, Clostridium botulinum
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Botulinum Toxins
  • Glucose