Molecular and Cellular Biology, August 2001, p. 5276-5285, Vol. 21, No. 15
Department of Medicine, Howard Hughes Medical
Institute, The Cox Institute, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104
Received 11 December 2000/Returned for modification 8 February
2001/Accepted 30 April 2001
In 3T3-L1 adipocytes, both insulin and endothelin 1 stimulate
glucose transport via translocation of the GLUT4 glucose carrier from
an intracellular compartment to the cell surface. Yet it remains
uncertain as to whether both hormones utilize identical pathways and to
what extent each depends on the heterotrimeric G protein G
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.15.5276-5285.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
ADP-Ribosylation Factor 6 Delineates Separate
Pathways Used by Endothelin 1 and Insulin for Stimulating
Glucose Uptake in 3T3-L1 Adipocytes
q as an
intermediary signaling molecule. In this study, we used a novel
inducible system to rapidly and synchronously activate expression of a
dominant inhibitory form of ADP-ribosylation factor 6, ARF6(T27N),
in 3T3-L1 adipocytes and assessed its effects on insulin- and
endothelin-stimulated hexose uptake. Expression of ARF6(T27N) in 3T3-L1
adipocytes was without effect on the ability of insulin to stimulate
either 2-deoxyglucose uptake or the translocation of GLUT4 or GLUT1 to
the plasma membrane. However, the same ARF6 inhibitory mutant blocked
the stimulation of hexose uptake and GLUT4 translocation in response to
either endothelin 1 or an activated form of G
q, G
q(Q209L). These
results suggest that endothelin stimulates glucose transport through a
pathway that is distinct from that utilized by insulin but is likely to
depend on both a heterotrimeric G protein from the Gq family and the
small G protein ARF6. These data are consistent with the interpretation that endothelin and insulin stimulate functionally different pools of
glucose transporters to be redistributed to the plasma membrane.
*
Corresponding author. Mailing address: Howard Hughes
Medical Institute, University of Pennsylvania Medical School, 415 Curie Blvd., Room 322 CRB, Philadelphia, PA 19104. Phone: (215) 898-5001. Fax: (215) 573-9138. E-mail:
birnbaum{at}mail.med.upenn.edu.
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