Source:http://linkedlifedata.com/resource/pubmed/id/19826102
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2009-11-25
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| pubmed:abstractText |
Skeletal muscle glucose transport is regulated via the canonical insulin-signaling cascade as well as by energy-sensing signals. 5'-AMP-activated protein kinase (AMPK) has been implicated in the energy status regulation of glucose transport. We determined the role of the AMPKgamma3 isoform in hypoxia-mediated energy status signaling and glucose transport in fast-twitch glycolytic extensor digitorum longus (EDL) muscle from AMPKgamma3-knockout (KO) mice and wild-type mice. Although hypoxia increased glucose transport (P < 0.001) in wild-type mice, this effect was attenuated in AMPKgamma3-KO mice (45% reduction, P < 0.01). The role of Ca(2+)-mediated signaling was tested using the Ca(2+)/calmodulin competitive inhibitor KN-93. KN-93 exposure reduced hypoxia-mediated glucose transport in AMPKgamma3-KO and wild-type mice (P < 0.05). To further explore the underlying signaling mechanisms, phosphorylation of CaMKII, AMPK, ACC, and TBC1D1/D4 as well as isoform-specific AMPK activity was determined. Basal and hypoxia-mediated phosphorylation of CaMKII, AMPK, and ACC as well as alpha1- and alpha2-associated AMPK activity was comparable between AMPKgamma3-KO and wild-type mice. KN-93 reduced hypoxia-mediated CaMKII phosphorylation in AMPKgamma3-KO and wild-type mice (P < 0.05), whereas phosphorylation of AMPK and ACC as well as alpha1- and alpha2-associated AMPK activity was unaltered. Hypoxia increased TBC1D1/D4 phosphorylation in AMPKgamma3-KO and wild-type mice (P < 0.001). KN-93 exposure prevented this effect in AMPKgamma3-KO, but not in wild-type mice. Taken together, we provide direct evidence for a role of the AMPKgamma3 isoform in hypoxia-mediated glucose transport in glycolytic muscle. Moreover, hypoxia-mediated TBC1D1/D4 phosphorylation was uncoupled from glucose transport in AMPKgamma3-KO mice, indicating that TBC1D1/D4-independent mechanisms contribute to glucose transport in skeletal muscle.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AMP-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Benzylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transport Proteins...,
http://linkedlifedata.com/resource/pubmed/chemical/KN 93,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Prkag3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Tbc1d1 protein, mouse
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1522-1555
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
297
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
E1388-94
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| pubmed:dateRevised |
2010-10-8
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| pubmed:meshHeading |
pubmed-meshheading:19826102-AMP-Activated Protein Kinases,
pubmed-meshheading:19826102-Animals,
pubmed-meshheading:19826102-Benzylamines,
pubmed-meshheading:19826102-Biological Transport,
pubmed-meshheading:19826102-Calcium,
pubmed-meshheading:19826102-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:19826102-Cell Hypoxia,
pubmed-meshheading:19826102-Female,
pubmed-meshheading:19826102-Glucose,
pubmed-meshheading:19826102-Glucose Transport Proteins, Facilitative,
pubmed-meshheading:19826102-Immunohistochemistry,
pubmed-meshheading:19826102-Male,
pubmed-meshheading:19826102-Mice,
pubmed-meshheading:19826102-Mice, Inbred C57BL,
pubmed-meshheading:19826102-Mice, Knockout,
pubmed-meshheading:19826102-Muscle, Skeletal,
pubmed-meshheading:19826102-Muscle Fibers, Fast-Twitch,
pubmed-meshheading:19826102-Nuclear Proteins,
pubmed-meshheading:19826102-Phosphorylation,
pubmed-meshheading:19826102-Protein Kinase Inhibitors,
pubmed-meshheading:19826102-Signal Transduction,
pubmed-meshheading:19826102-Sulfonamides
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| pubmed:year |
2009
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| pubmed:articleTitle |
Role of the AMPKgamma3 isoform in hypoxia-stimulated glucose transport in glycolytic skeletal muscle.
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| pubmed:affiliation |
Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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