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

Vitor A Lira; Quinlyn A Soltow; Jodi H D Long; Jenna L Betters; Jeff E Sellman; David S Criswell

doi:10.1152/ajpendo.00045.2007

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

Journal article

Open access

Peer reviewed

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

Vitor A Lira, Quinlyn A Soltow, Jodi H D Long, Jenna L Betters, Jeff E Sellman and David S Criswell

American journal of physiology: endocrinology and metabolism, Vol.293(4), pp.E1062-1068

10/2007

DOI: 10.1152/ajpendo.00045.2007

PMID: 17666490

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Abstract

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 microM) significantly increased GLUT4 mRNA ( approximately 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 approximately 50% (P < 0.05). GLUT4 protein expression was elevated 40% by 2 days treatment with 8-Br-cGMP, whereas 6 days treatment with 10 microM 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 microM) also induced significant phosphorylation of alpha-AMPK and acetyl-CoA carboxylase and translocation of phosphorylated alpha-AMPK to the nucleus. Furthermore, L6 myotubes exposed to 5-aminoimidazole-4-carboxamide-1-beta-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 approximately 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 approximately 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.

Cyclic GMP - pharmacology

Muscle, Skeletal - enzymology

Glucose Transporter Type 4 - genetics

Glucose Transporter Type 4 - metabolism

Signal Transduction

Nitric Oxide - pharmacology

Cells, Cultured

Nitric Oxide Synthase - antagonists & inhibitors

Rats

Muscle, Skeletal - metabolism

Enzyme Activation - drug effects

Rats, Sprague-Dawley

Aminoimidazole Carboxamide - pharmacology

Gene Expression Regulation - drug effects

Ribonucleotides - pharmacology

Animals

Aminoimidazole Carboxamide - analogs & derivatives

Models, Biological

Adenylate Kinase - metabolism

Muscle, Skeletal - drug effects

Female

Details

Title: Subtitle: Nitric oxide increases GLUT4 expression and regulates AMPK signaling in skeletal muscle
Creators: Vitor A Lira - Department of Applied Physiology and Kinesiology, Center for Exercise Science, Univ. of Florida, Gainesville, FL 32611, USA
Quinlyn A Soltow
Jodi H D Long
Jenna L Betters
Jeff E Sellman
David S Criswell
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.293(4), pp.E1062-1068
DOI: 10.1152/ajpendo.00045.2007
PMID: 17666490
NLM abbreviation: Am J Physiol Endocrinol Metab
ISSN: 0193-1849
eISSN: 1522-1555
Publisher: United States
Language: English
Date published: 10/2007
Academic Unit: Health, Sport, and Human Physiology
Record Identifier: 9984002349502771

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