The DOI matches its Crossref record; 35 of the 37 references it cites were found in a registry or an index.
The 5′-AMP-activated Protein Kinase γ3 Isoform Has a Key Role in Carbohydrate and Lipid Metabolism in Glycolytic Skeletal Muscle
Open accessAbstract
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.
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“Interestingly, transgenic mice harboring the R225Q mutation in AMPK γ3 subunit have higher AMPK activity and glycogen levels and are protected from diet-induced insulin resistance [4], which is a likely effect of increased fatty acid oxidation and subsequent reduction in skeletal muscle lipids.”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [4]
In the citing paper
“Whole-body γ3 KO mice have reduced AMPK activity at rest, during exercise and in response to fasting, but normal insulin sensitivity under basal conditions and glucose uptake during exercise [4,41].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [4]
In the citing paper
“Whole-body γ3 KO mice have reduced AMPK activity at rest, during exercise and in response to fasting, but normal insulin sensitivity under basal conditions and glucose uptake during exercise [4,41].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [4]
In the citing paper
“Although TBC1D1 expression or PAS phosphorylation was not assessed in skeletal muscle from β2 or γ3 KO mice, contraction-mediated glucose uptake was also normal [4,28], suggesting that the remaining subunit isoforms (likely contributing to maintained or elevated α1 AMPK activity) was sufficient to allow for normal glucose uptake.”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [4]
In the citing paper
“AMPK α2 KO and α2 KD and α2iTg mice have normal or only modest reductions in glucose uptake during contractions [4,26,31,32,118-120].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [4]
In the citing paper
“It has been proposed that glycogen depletion and AMPK activation may play a role in insulin sensitizing effects of exercise given AMPK γ3 KO and α2 KD mice have impaired glycogen resynthesis following exercise [4,31].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [4]
Citations
Cites
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Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
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A Mutation in PRKAG3 Associated with Excess Glycogen Content in Pig Skeletal Muscle
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Flagged first, then by citations
2 of the 37 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
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- Hayashi, 1998, Diabetes, 47, 1369
- Arad, 2002, J. Clin. Investig., 109, 357, 10.1172/JCI0214571 · DOI
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Cited by
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Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
“In mice in which the γ3 gene was deleted, glycogen resynthesis following exercise was reduced, whereas it was increased in the γ3 mutant transgenic animals (Barnes et al., 2004).”
BackgroundSteinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,672
PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624
Exercise, GLUT4, and skeletal muscle glucose uptake
Richter, E. A., & Hargreaves, M. (2013) · Physiological Reviews · doi:10.1152/physrev.00038.2012 · Cited by 1,407
“Activation of AMPK by AICAR in resting muscle results in increased glucose uptake (209), and this effect is lost when 2- or 3-AMPK subunits are deficient (21, 152, 216).”
The Human Obesity Gene Map: The 2005 Update
Rankinen, T., Zuberi, A., Chagnon, Y. C., Weisnagel, S. J., Argyropoulos, G., Walts, B., Pérusse, L., & Bouchard, C. (2006) · Obesity · doi:10.1038/oby.2006.71 · Cited by 1,119
Metadata
- Authors
- Barnes, B. R., Marklund, S., Steiler, T. L., Walter, M., Hjälm, Amarger, V., Mahlapuu, M., Leng, Y., Johansson, C., Galuska, D., Lindgren, K., Åbrink, M., Stapleton, D., Zierath, J. R., & Andersson, L.
- Affiliations
- Karolinska Institutet (SE)
- Swedish University of Agricultural Sciences (SE)
- Uppsala University (SE)
- Corresponding author
- Zierath, Juleen R.
- Andersson, Leif
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 279
- Issue
- 37
- Pages
- 38441-38447
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2147553969
- Cited by
- 317
- References
- 37
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 15 · 2019: 15 · 2018: 9 · 2017: 14 · 2016: 21 · 2015: 17 · 2014: 21 · 2013: 17 · 2012: 10
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Svenska Forskningsrådet Formas
- Karolinska Institutet
- Vetenskapsrådet
- Uppsala Universitet
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Glycogen Storage Diseases and Myoclonus
- Keywords
- AMPK, PRKAG3, skeletal muscle, glycogen resynthesis, physical activity, skeletal muscle glucose uptake, triglyceride accumulation, insulin resistance, high-fat diet, carbohydrate metabolism, lipid metabolism
- MeSH terms
- Animals, Blood Glucose, Glucose, Glycogen, Glycolysis, Insulin, Mice, Transgenic, Models, Genetic, Multienzyme Complexes, Protein Kinases, RNA, Messenger, Swine, Temperature, Transfection, Triglycerides, Protein Serine-Threonine Kinases, DNA, Complementary, Mice, Knockout, Muscle, Skeletal, COS Cells, Protein Isoforms, Mutation, Missense, Reverse Transcriptase Polymerase Chain Reaction, Lipid Metabolism, Mice, AMP-Activated Protein Kinases
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