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Title: Cyclic adenosine 3',5'-monophosphate regulates GLUT4 and GLUT1 glucose transporter expression and stimulates transcriptional activity of the GLUT1 promoter in muscle cells
Author: Viñals Canals, Francesc
Ferré, Josep
Fandos Espallargas, César
Santalucía Albi, Tomàs
Testar, Xavier
Palacín Prieto, Manuel
Zorzano Olarte, Antonio
Keywords: Fosfodiesterases
Monofosfat d'adenosina cíclic
Efectes secundaris dels medicaments
Adenylic acid
Drug side effects
Issue Date: Jun-1997
Publisher: Association for the Study of Internal Secretions
Abstract: We have previously reported that innervation-dependent basal contractile activity regulates in an inverse manner the expression of GLUT1 and GLUT4 glucose transporters in skeletal muscle. Based on the facts that muscle innervation decreases and muscle denervation increases cAMP levels, we investigated whether cAMP might mediate the effects of innervation/denervation on glucose transporter expression. Treatment of L6E9 myotubes with 8-bromo-cAMP, forskolin, or monobutyryl-8-bromo-cAMP led to a marked decrease in GLUT4 protein levels; 8-bromo-cAMP also diminished GLUT4 messenger RNA (mRNA), suggesting pretranslational repression. In contrast, L6E9 myoblasts and myotubes responded to 8-bromo-cAMP or forskolin by increasing the cell content of GLUT1 protein. Induction of GLUT1 protein was a consequence of the activation of different mechanisms in myoblast and myotube cells; whereas 8-bromo-cAMP treatment caused a substantial increase in GLUT1 mRNA in myoblasts, no change in GLUT1 mRNA was detected in myotubes. The increase in GLUT1 mRNA in L6E9 myoblasts induced by 8-bromo-cAMP was the result of transcriptional activation, as concluded from transfection analysis of 2.1 kilobases of the rat GLUT1 gene promoter fused to the bacterial chloramphenicol acetyltransferase gene. Furthermore, the stimulatory effect of 8-bromo-cAMP on the transcriptional activity of the GLUT1 promoter required a 33-bp sequence lying 5' upstream of the transcription start site. In all, cAMP inversely regulates GLUT4 and GLUT1 glucose transporter expression in muscle cells. Furthermore, our results suggest that down-regulation of GLUT4 expression and up-regulation of GLUT1 expression in muscle associated with denervation are partly attributable to cAMP.
Note: Reproducció del document publicat a:
It is part of: Endocrinology, 1997, vol. 138, num. 6, p. 2521-2529
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ISSN: 0013-7227
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Infermeria Fonamental i Medicoquirúrgica)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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