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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]
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Cites
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
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?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,440
Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036
Mu, J., Brozinick, J. T., Valladares, O., Bucan, M., & Birnbaum, M. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00251-9 · Cited by 924
Hayashi, T., Hirshman, M. F., Kurth, E. J., Winder, W. W., & Goodyear, L. J. (1998) · Diabetes · doi:10.2337/diab.47.8.1369 · Cited by 774
Scott, J. W., Hawley, S. A., Green, K. A., Anis, M., Stewart, G., Scullion, G. A., Norman, D. G., & Hardie, D. G. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19874 · Cited by 754
A Mutation in PRKAG3 Associated with Excess Glycogen Content in Pig Skeletal Muscle
Milan, D., Jeon, J., Looft, C., Amarger, V., Robic, A., Thelander, M., Rogel-Gaillard, C., Paul, S., Iannuccelli, N., Rask, L., et al. (2000) · Science · doi:10.1126/science.288.5469.1248 · Cited by 733
Self-citationActivation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases
Hong, S. P., Leiper, F. C., Woods, A., Carling, D., & Carlson, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533136100 · Cited by 617
Jørgensen, S. B., Viollet, B., Andreelli, F., Frøsig, C., Birk, J. B., Schjerling, P., Vaulont, S., Richter, E. A., & Wojtaszewski, J. F. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306205200 · Cited by 553
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
- Hawley, 2003, J. Biol.
- Hayashi, 1998, Diabetes, 47, 1369
- Arad, 2002, J. Clin. Investig., 109, 357, 10.1172/JCI0214571 · DOI
- Estrade, 1993, Comp. Biochem. Physiol., 104B, 321
- Monin, G., Brard, C., Vernin, P. & Naveau, J. (1992) in 38th International Congress on Meat Science and Technology, Vol. 3, pp. 391–394, Clermont-Ferrand, France
- Kozak, 1989, Mol. Cell. Biol., 9, 5073
- Estrade, 1994, Comp. Biochem. Physiol., 108, 295
Cited by
Sorted by citations
Items 101–200 of 317
High glycolytic potential does not predict low ultimate pH in pork
Scheffler, T. L., Scheffler, J. M., Kasten, S., Sosnicki, A. A., & Gerrard, D. E. (2013) · Meat Science · doi:10.1016/j.meatsci.2013.04.013 · Cited by 69
Liu, Y., Lai, Y., Hill, E. V., Tyteca, D., Carpentier, S., Ingvaldsen, A., Vertommen, D., Lantier, L., Foretz, M., Dequiedt, F., et al. (2013) · Biochemical Journal · doi:10.1042/bj20130644 · Cited by 67
Abdallah, M. A., Uchea, C., Chipman, J. K., & Harrad, S. J. (2014) · Environmental Science & Technology · doi:10.1021/es404644s · Cited by 67
The metabolic sensor AMPK: Twelve enzymes in one
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“Despite a higher af fi nity of g 3-CBS3 for AMP than g 1 [113], and an ability to associate with AMP mimetics (i.e., ZMP) [290], substantial evidence demonstrates AMP has negligible-to-mild allosteric activating effects toward g 3-AMPK [18,99,113,120,291 e 293].”
Diet, obesity and diabetes: a current update
Walker, C. G., Zariwala, M. G., Holness, M. J., & Sugden, M. C. (2006) · Clinical Science · doi:10.1042/cs20060150 · Cited by 62
The AMPK β2 Subunit Is Required for Energy Homeostasis during Metabolic Stress
Dasgupta, B., Ju, J.-S., Sasaki, Y., Liu, X., Jung, S.-R., Higashida, K., Lindquist, D. M., & Milbrandt, J. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05853-11 · Cited by 64
Fontanesi, L., Davoli, R., Costa, L. N., Beretti, F., Scotti, E., Tazzoli, M., Tassone, F., Colombo, M., Buttazzoni, L., & Russo, V. C. (2008) · Meat Science · doi:10.1016/j.meatsci.2008.03.022 · Cited by 61
Sibut, V., Hennequet‐Antier, C., Bihan-Duval, É. L., Marthey, S., Duclos, M. J. M. J., & Berri, C. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-112 · Cited by 64
“In mammalian species, including the pig, mouse and human, a major gene, PRKAG3 which encodes the g3 regulatory subunit of the AMP-activated protein kinase (AMPK), is responsible for variations in muscle glycogen content [6-10].”
BackgroundSpeirs, C., Williams, J. J. L., Riches‐Suman, K., Salt, I. P., & Palmer, T. M. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.10.001 · Cited by 61
Barnes, B. R., Long, Y. C., Steiler, T. L., Leng, Y., Galuska, D., Wojtaszewski, J. F. P., Andersson, L., & Zierath, J. R. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3484 · Cited by 60
“The creation and general metabolic characteristics of these animal models have been described previously (15).”
InfluentialSelf-citationDomestic animals as models for biomedical research
Andersson, L. (2015) · Upsala Journal of Medical Sciences · doi:10.3109/03009734.2015.1091522 · Cited by 56
Self-citationNilsson, E. C., Long, Y. C., Martinsson, S., Glund, S., García-Rovés, P. M., Svensson, T., Andersson, L., Zierath, J. R., & Mahlapuu, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510461200 · Cited by 58
Self-citationLefort, N., St.-Amand, E., Morasse, S., Côté, C. H., & Marette, A. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90362.2008 · Cited by 57
Zhang, C., Wang, Z., Bruce, H. L., Kemp, R. A., Charagu, P., Miar, Y., Yang, T., & Plastow, G. S. (2015) · BMC Genetics · doi:10.1186/s12863-015-0192-1 · Cited by 56
“All these processes are essential to maintain muscle membrane and myofibrillar protein integrity in the face of dramatic metabolic changes after exsanguination, such as the shift from aerobic to anaerobic glycolysis with anoxia and high body temperature, depletion of ATP, accumulation of lactate and hydrogen ions, and…”
Hingst, J. R., Kjøbsted, R., Birk, J. B., Eskesen, N. O., Larsen, M. R., Kido, K., Larsen, J. K., Kjeldsen, S. A. S., Fentz, J., Frøsig, C., et al. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101028 · Cited by 57
SNP variation in the promoter of the PRKAG3gene and association with meat quality traits in pig
Ryan, M. T., Hamill, R. M., O’Halloran, A. M., Davey, G. C., McBryan, J., Mullen, A. M., McGee, C., Gispert, M., Southwood, O. I., & Sweeney, T. (2012) · BMC Genetics · doi:10.1186/1471-2156-13-66 · Cited by 57
Jensen, T. E., Ross, F. A., Kleinert, M., Sylow, L., Knudsen, J. R., Gowans, G. J., Hardie, D. G., & Richter, E. A. (2015) · Biochemical Journal · doi:10.1042/bj20141142 · Cited by 55
Insight on Transcriptional Regulation of the Energy Sensing AMPK and Biosynthetic mTOR Pathway Genes
Sukumaran, A., Choi, K., & Dasgupta, B. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00671 · Cited by 62
“…when AMPK was shown to phosphorylate and increase glycogen phosphorylase activity (the rate limiting enzyme for glycogenolysis) (Carling and Hardie, 1989; Young et al., 1996), although this was later disputed by other studies (Viollet et al., 2003a,b; Barnes et al., 2004; Jorgensen et al., 2005).”
ResultMyosin heavy chain isoform content and energy metabolism can be uncoupled in pig skeletal muscle
Park, S. K., Gunawan, A. M., Scheffler, T. L., Grant, A. L., & Gerrard, D. E. (2008) · Journal of Animal Science · doi:10.2527/jas.2008-1269 · Cited by 54
“Barnes et al. (2004, 2005) showed that the R225Q mutation is a loss-of-function mutation that abolishes AMP dependence, resulting in greater basal AMPK activity.”
BackgroundMcGee, S. L., Swinton, C., Morrison, S., Gaur, V., Campbell, D. E., Jørgensen, S. B., Kemp, B. E., Baar, K., Steinberg, G. R., & Hargreaves, M. (2014) · The FASEB Journal · doi:10.1096/fj.14-249359 · Cited by 52
“In addition, activation of AMPK, either genetically or pharmacologically, results in gene expression responses that are remarkably similar to those induced by exercise (16, 17).”
BackgroundScheffler, T. L., Scheffler, J. M., Park, S., Kasten, S., Wu, Y., McMillan, R. P., Hulver, M. W., Frisard, M. I., & Gerrard, D. E. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00002.2013 · Cited by 51
Copenhafer, T. L., Richert, B., Schinckel, A., Grant, A. L., & Gerrard, D. E. (2006) · Meat Science · doi:10.1016/j.meatsci.2006.02.015 · Cited by 51
Post-Translational Modifications of the Energy Guardian AMP-Activated Protein Kinase
Ovens, A. J., Scott, J. W., Langendorf, C. G., Kemp, B. E., Oakhill, J. S., & Smiles, W. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031229 · Cited by 50
“For example, the α2β2γ3 complex that is exclusively expressed in skeletal muscle (predominantly in white, glycolytic (fast twitch/type II) fibres [15]) is preferentially activated by high-intensity exercise [16,17].”
BackgroundPotentiation of insulin-stimulated glucose transport by the AMP-activated protein kinase
Ju, J.-S., Gitcho, M. A., Casmaer, C. A., Patil, P. B., Han, D.-G., Spencer, S. A., & Fisher, J. S. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00269.2006 · Cited by 47
Viollet, B., & Foretz, M. (2016) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-319-43589-3 · Cited by 48
AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis
Smith, T. K. T., Townsend, L. K., Smiles, W. J., Oakhill, J. S., Fullerton, M. D., & Steinberg, G. R. (2026) · Nature Metabolism · doi:10.1038/s42255-025-01442-3 · Cited by 55
Fritzen, A. M., Lundsgaard, A., Jeppesen, J. F., Christiansen, M. L. B., Biensø, R. S., Dyck, J. R. B., Pilegaard, H., & Kiens, B. (2015) · The Journal of Physiology · doi:10.1113/jp270821 · Cited by 47
How is AMPK activity regulated in skeletal muscles during exercise?
Jørgensen, S. B. (2008) · Frontiers in bioscience · doi:10.2741/3102 · Cited by 45
“For instance, some observations (60, 85, 112) suggest that AMPK has a partial role in regulating glucose uptake in ex vivo contracting muscles whereas others (7, 33, 65) have found AMPK to be redundant.”
BackgroundHormones, Metabolism and the Benefits of Exercise
(2017) · Research and Perspectives in Endocrine Interactions · doi:10.1007/978-3-319-72790-5 · Cited by 44
Deshmukh, A. S., Treebak, J. T., Long, Y. C., Viollet, B., Wojtaszewski, J. F. P., & Zierath, J. R. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0448 · Cited by 44
“The content of the prebuffer has been described previously (21, 25).”
BackgroundMethodResultInfluentialSelf-citationCameron, K. O., & Kurumbail, R. G. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.09.065 · Cited by 44
Aoi, W., Hirano, N., Lassiter, D. G., Björnholm, M., Chibalin, A., Sakuma, K., Tanimura, Y., Mizushima, K., Takagi, T., Naito, Y., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900453r · Cited by 43
Self-citationSaner, N. J., Bishop, D. J., & Bartlett, J. D. (2018) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2017.01.001 · Cited by 41
Beck Jørgensen, S., O’Neill, H. M., Hewitt, K., Kemp, B. E., & Steinberg, G. R. (2009) · Diabetologia · doi:10.1007/s00125-009-1483-8 · Cited by 42
Keipert, S., Ost, M., Chadt, A., Voigt, A., Ayala, V., Portero‐Otín, M., Pamplona, R., Al‐Hasani, H., & Klaus, S. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00518.2012 · Cited by 43
Influence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle
Long, Y. C., & Zierath, J. R. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90259.2008 · Cited by 41
“The advantage of activating AMPK has been highlighted by the findings that transgenic mice overexpressing an activated form of the AMPK 3 subunit are protected against dietary-induced skeletal muscle insulin resistance (6) and, at the local level in isolated skeletal muscle, display fatigue resistance in response to i…”
BackgroundInfluentialSelf-citationPostmortem Changes in Pork Muscle Protein Phosphorylation in Relation to the RN Genotype
Lametsch, R., Larsen, M. R., Essén-Gustavsson, B., Jensen‐Waern, M., Lundström, K., & Lindahl, G. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf201936h · Cited by 42
Exercise in rats does not alter hypothalamic AMP-activated protein kinase activity
Andersson-Hall, U. K., Treebak, J. T., Nielsen, J. N., Smith, K. L., Abbott, C. R., Small, C. J., Carling, D., & Richter, E. A. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.02.027 · Cited by 43
Tohyama, D., & Yamaguchi, A. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.126 · Cited by 41
Chen, Q., Xie, B., Zhu, S., Rong, P., Sheng, Y., Ducommun, S., Chen, L., Quan, C., Li, M., Sakamoto, K., et al. (2016) · Diabetologia · doi:10.1007/s00125-016-4151-9 · Cited by 41
Aoi, W., Inoüe, R., Mizushima, K., Honda, A., Björnholm, M., Takagi, T., & Naito, Y. (2023) · iScience · doi:10.1016/j.isci.2023.106251 · Cited by 45
Effects of AMPK Activation on Insulin Sensitivity and Metabolism in Leptin-Deficient ob/ob Mice
Tom, R. Z., García-Rovés, P. M., Sjögren, R. J. O., Jiang, L. Q., Holmström, M., Deshmukh, A. S., Vieira, E. C., Chibalin, A., Björnholm, M., & Zierath, J. R. (2014) · Diabetes · doi:10.2337/db13-0670 · Cited by 40
“2A), consistent with our previously observation that glucose tolerance is unaltered in lean WT and γ3 R225Q transgenic mice (17).”
InfluentialSelf-citationZhong, W., Jiang, Z., Zheng, C., Lin, Y., Yang, L., & Zou, S. (2010) · British Journal Of Nutrition · doi:10.1017/s0007114510003181 · Cited by 40
Yu, H., Hirshman, M. F., FUJII, N. L., Pomerleau, J. M., Peter, L. E., & Goodyear, L. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00073.2006 · Cited by 38
“In contrast to the present report, glycogen was not significantly altered in WT 3 transgenic mice in the resting state; however, there was a tendency toward increased concentrations during recovery from exercise (6).”
BackgroundMethodResultInfluentialYarar‐Fisher, C., Bickel, C. S., Windham, S. T., McLain, A., & Bamman, M. M. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00122.2013 · Cited by 38
“For example, AMPK promotes GLUT-4-dependent glucose transport in skeletal muscle in response to contractile activity (4).”
BackgroundEffect of 6-gingerol on AMPK- NF-κB axis in high fat diet fed rats
Hashem, R. M., Rashed, L. A., Hassanin, K. M. A., Hetta, M. H., & Ahmed, A. O. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.01.035 · Cited by 38
The importance of the ZBED6‐IGF2 axis for metabolic regulation in mouse myoblast cells
Younis, S., Naboulsi, R., Wang, X., Cao, X., Larsson, M., Sargsyan, E., Bergsten, P., Welsh, N., & Andersson, L. (2020) · The FASEB Journal · doi:10.1096/fj.201901321r · Cited by 38
Self-citationProteomic profile of dry-cured ham relative to PRKAG3 or CAST genotype, level of salt and pastiness
Škrlep, M., Čandek‐Potokar, M., Mandelc, S., Javornik, B., Gou, P., Chambon, C., & Santé-Lhoutellier, V. (2011) · Meat Science · doi:10.1016/j.meatsci.2011.02.025 · Cited by 37
Moffat, C., & Harper, M. (2010) · IUBMB Life · doi:10.1002/iub.387 · Cited by 38
“The R225Q mice exhibited enhanced glucose uptake, corroborating observations within the RN(2) pigs; mice were also protected against insulin resistance and triglyceride accumulation in muscle when fed a high fat diet, an effect that was absent in the KO mice (41).”
Duan, Y., Li, F., Wang, W., Guo, Q., Wen, C., & Yin, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.22205 · Cited by 41
“com/oncotarget metabolic dysregulation [7, 26].”
Zhang, P., Li, Q., Wu, Y., Zhang, Y., Zhang, B., & Zhang, H. (2022) · Scientific Reports · doi:10.1038/s41598-022-06868-3 · Cited by 38
Localisation of AMPK γ subunits in cardiac and skeletal muscles
Pintér, K., Grignani, R., Watkins, H. C., & Redwood, C. S. (2013) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-013-9359-4 · Cited by 39
“…abundant and shows wide tissue expression, as does c2 whereas the c3 isoform is almost exclusively expressed in skeletal muscle (Lang et al. 2000; Barnes et al. 2004; K. Pinter R. T. Grignani H. Watkins C. Redwood (&) Department of Cardiovascular Medicine, John Radcliffe Hospital, University of…”
Hu, D., Hu, D., Liu, L., Barr, D. A., Liu, Y., Balderrábano-Saucedo, N., Wang, B., Zhu, F., Xue, Y., Wu, S., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102723 · Cited by 36
Jensen, T. E., Leutert, R., Rasmussen, S. T., Mouatt, J. R., Christiansen, M. L. B., Jensen, B. R., & Richter, E. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031054 · Cited by 36
Foretz, M., Hébrard, S., Guihard, S., Leclerc, J., Cruzeiro, M. D., Hamard, G., Niedergang, F., Gaudry, M., & Viollet, B. (2010) · The FASEB Journal · doi:10.1096/fj.10-169383 · Cited by 40
“Disruption of the 3-subunit gene in mice results in changes to carbohydrate and lipid metabolism in white skeletal muscle (20).”
BackgroundGlund, S., Treebak, J. T., Long, Y. C., Barrès, R., Viollet, B., Wojtaszewski, J. F. P., & Zierath, J. R. (2008) · Endocrinology · doi:10.1210/en.2008-1204 · Cited by 35
Self-citationKitzmann, M., Lantier, L., Hébrard, S., Mercier, J. G., Foretz, M., & Aguer, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.007 · Cited by 34
Diacylglycerol kinase-δ regulates AMPK signaling, lipid metabolism, and skeletal muscle energetics
Jiang, L. Q., Barbosa, T. D. C., Massart, J., Deshmukh, A. S., Löfgren, L., Duque-Guimaraes, D. E., Ozilgen, A., Osler, M. E., Chibalin, A., & Zierath, J. R. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00209.2015 · Cited by 35
Self-citationGranlund, A., Jensen-Waern, M., & Essén-Gustavsson, B. (2011) · Acta Veterinaria Scandinavica · doi:10.1186/1751-0147-53-20 · Cited by 37
“Studies on transgenic mice (Tg-Prkag3) have shown that the PRKAG3 mutation is associated with a greater basal AMPK activity [22].”
BackgroundLi, L., Zhang, H., Yao, Y., Yang, Z., & Ma, H. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b07287 · Cited by 32
Fediuc, S., Gaidhu, M. P., & Ceddia, R. B. (2006) · Endocrinology · doi:10.1210/en.2006-0480 · Cited by 33
The Energy Sensor AMPK: Adaptations to Exercise, Nutritional and Hormonal Signals
Viollet, B. (2017) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-319-72790-5_2 · Cited by 34
“Of interest, in contrast to other AMPK isoforms, expression of the AMPK3 isoform is restricted to the fast-twitch glycolytic skeletal muscle, suggesting a particular role for AMPK3-containing complexes to handle metabolic challenges in skeletal muscle (Barnes et al. 2004).”
BackgroundRole of AMPK in skeletal muscle gene adaptation in relation to exercise
Jørgensen, S. B., Jensen, T. E., & Richter, E. A. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-079 · Cited by 33
“2007a) or question (Barnes et al. 2004; Jorgensen et al. 2004; Fujii et al. 2005) a role of AMPK.”
BackgroundExendin-4 increases oxygen consumption and thermogenic gene expression in muscle cells
Choung, J.-S., Lee, Y.-S., & Jun, H.-S. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0078 · Cited by 31
Louden, E. D., Chi, M. M.-Y., & Moley, K. H. (2008) · Reproduction · doi:10.1530/rep-08-0161 · Cited by 31
“The resulting doublet in the compound C-treated cells may be the result of a protease sensitive site within pAMPK g-subunit (Barnes et al. 2004).”
BackgroundRhein, P., Desjardins, E. M., Rong, P., Ahwazi, D., Bonhoure, N., Stolte, J., Santos, M. D., Ovens, A. J., Ehrlich, A. M., Garcia, J. L. S., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101228 · Cited by 28
“However, the previously generated g3 deficient mice did not exhibit significantly reduced expression or activity of AMPKa2 [25], the predominant a-catalytic isoform in skeletal muscle.”
BackgroundResultInfluentialWeyrich, P., Machicao, F. E., Staiger, H., Simon, P. D., Thamer, C., Machann, J., Schick, F., Guirguis, A., Fritsche, A., Stefan, N., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0788-8 · Cited by 30
“under the control of a muscle-specific promoter [ 11 ].”
BackgroundCrawford, S. A., Costford, S. R., Aguer, C., Thomas, S. C., deKemp, R. A., DaSilva, J. N., Lafontaine, D., Kendall, M. S., Dent, R., Beanlands, R. S., et al. (2010) · Diabetologia · doi:10.1007/s00125-010-1788-7 · Cited by 29
“The observed decrease in IMTG content, and increases in glycogen content and oxidative capacity in human myotubes with the PRKAG3 R225W mutation are consistent with the previous animal models with the homologous R225Q mutation [19, 23].”
BackgroundResultInfluentialAlkhateeb, H. H., Chabowski, A., Glatz, J. F. C., Gurd, B. J., Luiken, J. J. F. P., & Bonen, A. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90908.2008 · Cited by 28
“However, questions have been raised recently as to whether AMPK activation is required to stimulate fatty acid oxidation (21, 25, 26, 52, 60, 62), and other studies have shown that glucose uptake is not impaired in mice with an AMPK deficiency (3, 27, 41).”
BackgroundOst, M., Werner, F., Dokas, J., Klaus, S., & Voigt, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094689 · Cited by 27
Schönke, M., Massart, J., & Zierath, J. R. (2018) · Journal of Lipid Research · doi:10.1194/jlr.d082370 · Cited by 27
“AMPK activation increases the abundance of mitochondrial enzymes and lipid metabolism in skeletal muscle (28, 35, 36).”
BackgroundMethodInfluentialSelf-citationTBC1D4-S711 Controls Skeletal Muscle Insulin Sensitization After Exercise and Contraction
Kjøbsted, R., Kristensen, J. M., Eskesen, N. O., Kido, K., Fjorder, K., Damgaard, D. F., Larsen, J. K., Andersen, N. R., Birk, J. B., Gudiksen, A., et al. (2023) · Diabetes · doi:10.2337/db22-0666 · Cited by 27
Pintér, K., Grignani, R., Czibik, G., Farza, H., Watkins, H. C., & Redwood, C. S. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.05.017 · Cited by 30
“However, it has to be noted that no conduction defects have been observed in either pigs with γ3 mutations [20,27] or in the transgenic mice that mimic the porcine phenotype [28,29] suggesting that γ2 may either have a different or more significant role during development in this region.”
Lassiter, D. G., Sjögren, R. J. O., Gabriel, B. M., Krook, A., & Zierath, J. R. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.07.004 · Cited by 25
Self-citationAMPKγ3 Controls Muscle Glucose Uptake in Recovery From Exercise to Recapture Energy Stores
Kido, K., Eskesen, N. O., Henriksen, N. S., Onslev, J., Kristensen, J. M., Larsen, M. R., Hingst, J. R., Knudsen, J. R., Birk, J. B., Andersen, N. R., et al. (2023) · Diabetes · doi:10.2337/db23-0358 · Cited by 25
“5 h after a swimming exercise (13), but these findings were not associated with a difference in muscle glucose uptake between WT and AMPKg3 KO mice (29).”
NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
Chubanava, S., Karavaeva, I. E., Ehrlich, A. M., Justicia, R. M., Basse, A. L., Kulik, I., Dalbram, E., Ahwazi, D., Heaselgrave, S. R., Trôst, K., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.04.002 · Cited by 30
Self-citationFighting obesity: When muscle meets fat
Yang, X., Bi, P., & Kuang, S. (2014) · Adipocyte · doi:10.4161/21623945.2014.964075 · Cited by 25
Past strategies and future directions for identifying AMP-activated protein kinase (AMPK) modulators
Sinnett, S. E., & Brenman, J. E. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.02.008 · Cited by 26
Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity
Kjøbsted, R., Wojtaszewski, J. F. P., & Treebak, J. T. (2016) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-319-43589-3_5 · Cited by 26
Characterization of the bovine PRKAG3 gene: structure, polymorphism, and alternative transcripts
Roux, M., Nizou, A., Forestier, L., Ouali, A., Levéziel, H. H., & Amarger, V. (2006) · Mammalian Genome · doi:10.1007/s00335-005-0093-0 · Cited by 24
“The implication of the c3 subunit in AMPK-dependent glucose uptake in skeletal muscle and glycogen resynthesis after exercise was demonstrated by using AMPK c3 knockout mice and transgenic mice overexpressing the mutated (225Q) c3 subunit (Barnes et al. 2004).”
BackgroundSelf-citationPutman, C. T., Martins, K. J. B., Gallo, M. E., Lopaschuk, G. D., Pearcey, J. A., MacLean, I. M., Saranchuk, R. J., & Pette, D. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00609.2006 · Cited by 25
Eskesen, N. O., Kjøbsted, R., Larsen, M. R., Birk, J. B., Andersen, N. R., Albuquerque, B., Schjerling, P., Miller, R., Carling, D., Pehmøller, C. K., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101259 · Cited by 23
Application of serial analysis of gene expression to the study of human genetic disease
Horan, M. P. (2009) · Human Genetics · doi:10.1007/s00439-009-0719-5 · Cited by 23
“This suggests the AMPK- 3 R225Q variant may be utilised as a putative therapeutic agent for the treatment of metabolic disorders including insulin resistance and diabetes (Barnes et al. 2004; Garcia-Roves et al. 2008).”
Molecular Pathogenesis of Familial Wolff‐Parkinson‐White Syndrome.
Miyamoto, L. (2018) · The Journal of Medical Investigation · doi:10.2152/jmi.65.1 · Cited by 23
Huang, H., Scheffler, T. L., Gerrard, D. E., Larsen, M. R., & Lametsch, R. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00294 · Cited by 23
Moreno, D., Viana, R., & Sanz, P. (2009) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2009.07.002 · Cited by 28
A muscle-specific UBE2O/AMPKα2 axis promotes insulin resistance and metabolic syndrome in obesity
Vila, I. K., Park, M. K., Setijono, S. R., Yao, Y., Kim, H., Badin, P.-M., Choi, S., Narkar, V. A., Choi, S., Chung, J., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.128269 · Cited by 23
Xu, J., Chen, L., Tang, L., Chang, L., Liu, S., Tan, J., Chen, Y., Ren, Y., Liang, F., & Cui, J. (2015) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-015-0667-7 · Cited by 22
“Activation of AMPK using AICAR can increase glucose uptake and fatty acid oxidation in obese diabetic rodents [37, 38] and humans [39–43], which validates the therapeutic potential of an AMPK activator.”
BackgroundCherel, P., Pires, J., Glénisson, J., Denis Milan, A., Iannuccelli, N., Herault, F., Damon, M., & Roy, P. L. (2011) · BMC Genetics · doi:10.1186/1471-2156-12-76 · Cited by 22
“While physiological effects of the PRKAG3 Gln allele on muscle glycogen content have been experimentally validated in a murine knock-in model [30], our data also highlight a causative effect of PRKAG3 mutation on meat colour that cannot be analyzed in a mouse model and has been associated with PRKAG3 mutation carriers…”
BackgroundSkeletal muscle AMPK is essential for the maintenance of FNDC5 expression
Lally, J., Ford, R. J., Johar, J., Crane, J. D., Kemp, B. E., & Steinberg, G. R. (2015) · Physiological Reports · doi:10.14814/phy2.12343 · Cited by 21
“2010) and others (Barnes et al. 2004; Jorgensen et al. 2004) have observed, it failed to increase FNDC5 expression.”
BackgroundModulation of mitochondrial dysfunction for treatment of disease
Webb, M., Sideris, D. P., & Biddle, M. M. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.03.041 · Cited by 21
IL-6 is not essential for exercise-induced increases in glucose uptake
O’Neill, H. M., Palanivel, R., Wright, D. C., MacDonald, T. L., Lally, J., Schertzer, J. D., & Steinberg, G. R. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00946.2012 · Cited by 20
Targeting of AMP-activated protein kinase: prospects for computer-aided drug design
Kim, J., Yang, G., & Ha, J. (2016) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2017.1255194 · Cited by 21
“Indeed, the effect of AMPK in glucose uptake in the skeletal muscle was significantly ablated in animal, where a gene for each subunit was knocked out, implying that this AMPK complex is critical for glucose uptake [36 – 38].”
BackgroundBao, S., Briscoe, V. J., Tate, D. B., & Davis, S. N. (2009) · Diabetes · doi:10.2337/db09-0382 · Cited by 19
“Much recent work has demonstrated the importance of AMP-activated protein kinase (AMPK) as a key regulator of carbohydrate and lipid metabolism during exercise (45).”
BackgroundHemin Improves Insulin Sensitivity in Skeletal Muscle in High Fat–Fed Mice
Ju, T.-J., Kwon, W.-Y., Kim, Y., Kim, J., Kim, Y., Lee, I., & Park, S. (2014) · Journal of Pharmacological Sciences · doi:10.1254/jphs.14003fp · Cited by 19
Kostovski, E., Boon, H., Hjeltnes, N., Lundell, L. S., Ahlsén, M., Chibalin, A., Krook, A., Iversen, P. O., & Widegren, U. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00132.2013 · Cited by 19
“4) ASIA Motor score NA 26 (4) 19 (4)* 21 (5)* 24 (5)* 40 (12) 72 (6) 81 (2) Injury level C7 NA 1 0 0 C6 NA 4 1 1 C5 NA 1 6 5”
BackgroundInfluentialGranlund, A., Kotova, O., Benziane, B., Galuska, D., Jensen‐Waern, M., Chibalin, A., & Essén-Gustavsson, B. (2009) · Experimental Physiology · doi:10.1113/expphysiol.2009.051326 · Cited by 19
Self-citationReciprocity Between Skeletal Muscle AMPK Deletion and Insulin Action in Diet-Induced Obese Mice
Admin, A., Lantier, L., Williams, I. M., Williams, I. M., Guérin, A., Bracy, D. P., Goelzer, M., Foretz, M., Viollet, B., Hughey, C. C., et al. (2020) · Diabetes · doi:10.2337/db19-1074 · Cited by 21
“This may be directly linked to the critical importance of AMPK in the control of glycogen mass (33-40).”
BackgroundLendoye, E., Sibille, B., Rousseau, A., Murdaca, J., Grimaldi, P. A., & Lopez, P. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0504 · Cited by 18
Davoli, R., Schivazappa, C., Zambonelli, P., Braglia, S., Rossi, A., & Virgili, R. (2016) · Meat Science · doi:10.1016/j.meatsci.2016.11.018 · Cited by 18
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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