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J Biol Chem, Vol. 274, Issue 19, 13563-13568, May 7, 1999
Serotonin (5-Hydroxytryptamine), a Novel Regulator of Glucose
Transport in Rat Skeletal Muscle
Eric
Hajduch,
Franck
Rencurel,
Anudharan
Balendran ,
Ian H.
Batty§,
C. Peter
Downes§, and
Harinder S.
Hundal
From the Departments of Anatomy and Physiology and
§ Biochemistry and the Medical Research
Council Protein Phosphorylation Unit, The University of
Dundee, Dundee DD1 4HN, Scotland
In this study we show that serotonin
(5-hydroxytryptamine (5-HT)) causes a rapid stimulation in glucose
uptake by ~50% in both L6 myotubes and isolated rat skeletal muscle.
This activation is mediated via the 5-HT2A receptor,
which is expressed in L6, rat, and human skeletal muscle. In L6 cells,
expression of the 5-HT2A receptor is developmentally
regulated based on the finding that receptor abundance increases by
over 3-fold during differentiation from myoblasts to myotubes.
Stimulation of the 5-HT2A receptor using methylserotonin
(m-HT), a selective 5-HT2A agonist, increased muscle
glucose uptake in a manner similar to that seen in response to 5-HT.
The agonist-mediated stimulation in glucose uptake was attributable to
an increase in the plasma membrane content of GLUT1, GLUT3, and GLUT4.
The stimulatory effects of 5-HT and m-HT were suppressed in the
presence of submicromolar concentrations of ketanserin (a selective
5-HT2A antagonist) providing further evidence that the
increase in glucose uptake was specifically mediated via the
5-HT2A receptor. Treatment of L6 cells with insulin resulted in tyrosine phosphorylation of IRS1, increased cellular production of phosphatidylinositol 3,4,5-phosphate and a 41-fold activation in protein kinase B (PKB/Akt) activity. In contrast, m-HT
did not modulate IRS1, phosphoinositide 3-kinase, or PKB activity. The
present results indicate that rat and human skeletal muscle both
express the 5-HT2A receptor and that 5-HT and specific 5-HT2A agonists can rapidly stimulate glucose uptake in
skeletal muscle by a mechanism which does not depend upon components
that participate in the insulin signaling pathway.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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