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The 5'-AMP-activate...
The 5'-AMP-activated protein kinase gamma3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle
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Barnes, Brian R (författare)
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Marklund, Stefan (författare)
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Steiler, Tatiana L (författare)
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Walter, Mark (författare)
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Hjälm, Göran (författare)
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Amarger, Valerie (författare)
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Mahlapuu, Margit (författare)
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Leng, Ying (författare)
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Johansson, Carina (författare)
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- Galuska, Dana (författare)
- Karolinska Institutet
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Lindgren, Kerstin (författare)
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Åbrink, Magnus (författare)
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Stapleton, David (författare)
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- Zierath, Juleen R (författare)
- Karolinska Institutet
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- Andersson, Leif (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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(creator_code:org_t)
- 2004
- 2004
- Engelska.
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 279:37, s. 38441-38447
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 5'-AMP-activated protein kinase (AMPK) is a metabolic stress sensor present in all eukaryotes. A dominant missense mutation (R225Q) in pig PRKAG3, encoding the muscle-specific gamma3 isoform, causes a marked increase in glycogen content. To determine the functional role of the AMPK gamma3 isoform, we generated transgenic mice with skeletal muscle-specific expression of wild type or mutant (225Q) mouse gamma3 as well as Prkag3 knockout mice. Glycogen resynthesis after exercise was impaired in AMPK gamma3 knock-out mice and markedly enhanced in transgenic mutant mice. An AMPK activator failed to increase skeletal muscle glucose uptake in AMPK gamma3 knock-out mice, whereas contraction effects were preserved. When placed on a high fat diet, transgenic mutant mice but not knock-out mice were protected against excessive triglyceride accumulation and insulin resistance in skeletal muscle. Transfection experiments reveal the R225Q mutation is associated with higher basal AMPK activity and diminished AMP dependence. Our results validate the muscle-specific AMPK gamma3 isoform as a therapeutic target for prevention and treatment of insulin resistance.
Nyckelord
- Animals
- Blood Glucose/metabolism
- COS Cells
- DNA; Complementary/metabolism
- Glucose/metabolism
- Glycogen/metabolism
- Glycolysis
- Insulin/metabolism
- Lipids/*metabolism
- Mice
- Mice; Knockout
- Mice; Transgenic
- Models; Genetic
- Multienzyme Complexes/*chemistry/*genetics
- Muscle; Skeletal/*metabolism
- Mutation; Missense
- Protein Isoforms
- Protein Kinases/*chemistry/*genetics
- Protein-Serine-Threonine Kinases/*chemistry/*genetics
- RNA; Messenger/metabolism
- Research Support; Non-U.S. Gov't
- Reverse Transcriptase Polymerase Chain Reaction
- Swine
- Temperature
- Transfection
- Triglycerides/metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Barnes, Brian R
-
Marklund, Stefan
-
Steiler, Tatiana ...
-
Walter, Mark
-
Hjälm, Göran
-
Amarger, Valerie
-
visa fler...
-
Mahlapuu, Margit
-
Leng, Ying
-
Johansson, Carin ...
-
Galuska, Dana
-
Lindgren, Kersti ...
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Åbrink, Magnus
-
Stapleton, David
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Zierath, Juleen ...
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Andersson, Leif
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visa färre...
- Artiklar i publikationen
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Journal of Biolo ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet