HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/E1062    most recent 00045.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Lira, V. A. Articles by Criswell, D. S. Search for Related Content PubMed PubMed Citation Articles by Lira, V. A. Articles by Criswell, D. S.

Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle

Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, Florida

Submitted 17 January 2007 ; accepted in final form 29 July 2007

Nitric oxide (NO) and 5'-AMP-activated protein kinase (AMPK) are involved in glucose transport and mitochondrial biogenesis in skeletal muscle. Here, we examined whether NO regulates the expression of the major glucose transporter in muscle (GLUT4) and whether it influences AMPK-induced upregulation of GLUT4. At low levels, the NO donor S-nitroso-N-penicillamine (SNAP, 1 and 10 µM) significantly increased GLUT4 mRNA (3-fold; P < 0.05) in L6 myotubes, and cotreatment with the AMPK inhibitor compound C ablated this effect. The cGMP analog 8-bromo-cGMP (8-Br-cGMP, 2 mM) increased GLUT4 mRNA by 50% (P < 0.05). GLUT4 protein expression was elevated 40% by 2 days treatment with 8-Br-cGMP, whereas 6 days treatment with 10 µM SNAP increased GLUT4 expression by 65%. Cotreatment of cultures with the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one prevented the SNAP-induced increase in GLUT4 protein. SNAP (10 µM) also induced significant phosphorylation of -AMPK and acetyl-CoA carboxylase and translocation of phosphorylated -AMPK to the nucleus. Furthermore, L6 myotubes exposed to 5-aminoimidazole-4-carboxamide-1--D-ribofuranoside (AICAR) for 16 h presented an approximately ninefold increase in GLUT4 mRNA, whereas cotreatment with the non-isoform-specific NOS inhibitor N^G-nitro-L-arginine methyl ester, prevented 70% of this effect. In vivo, GLUT4 mRNA was increased 1.8-fold in the rat plantaris muscle 12 h after AICAR injection, and this induction was reduced by 50% in animals cotreated with the neuronal and inducible nitric oxide synthases selective inhibitor 1-(2-trifluoromethyl-phenyl)-imidazole. We conclude that, in skeletal muscle, NO increases GLUT4 expression via a cGMP- and AMPK-dependent mechanism. The data are consistent with a role for NO in the regulation of AMPK, possibly via control of cellular activity of AMPK kinases and/or AMPK phosphatases.

5-aminoimidazole-4-carboxamide-1--D-ribofuranoside; guanosine 3',5'-cyclic monophosphate; L6 myotubes; compound C; N^G-nitro-L-arginine methyl ester; glucose transporter 4; adenosine 5'-monophosphate-activated protein kinase

This article has been cited by other articles:

				J. A. Drenning, V. A. Lira, C. G. Simmons, Q. A. Soltow, J. E. Sellman, and D. S. Criswell Nitric oxide facilitates NFAT-dependent transcription in mouse myotubes Am J Physiol Cell Physiol, April 1, 2008; 294(4): C1088 - C1095. [Abstract] [Full Text] [PDF]

				H. J. Green, T. A. Duhamel, G. P. Holloway, J. W. Moule, D. W. Ranney, A. R. Tupling, and J. Ouyang Rapid upregulation of GLUT-4 and MCT-4 expression during 16 h of heavy intermittent cycle exercise Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R594 - R600. [Abstract] [Full Text] [PDF]