The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice

Journal article

Marcinko, Katarina, Bujak, Adam L., Lally, James S. V., Ford, Rebecca J., Wong, Tammy H., Smith, Brennan K., Kemp, Bruce Ernest, Jenkins, Yonchu, Li, Wei, Kinsella, Todd M., Hitoshi, Yasumichi and Steinberg, Gregory R.. (2015). The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice. Molecular Metabolism. 4(9), pp. 643 - 651. https://doi.org/10.1016/j.molmet.2015.06.002
AuthorsMarcinko, Katarina, Bujak, Adam L., Lally, James S. V., Ford, Rebecca J., Wong, Tammy H., Smith, Brennan K., Kemp, Bruce Ernest, Jenkins, Yonchu, Li, Wei, Kinsella, Todd M., Hitoshi, Yasumichi and Steinberg, Gregory R.
Abstract

Objective: Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatment improves insulin sensitivity and exercise capacity in obese insulin resistant mice and whether skeletal muscle AMPK was important for mediating potential effects. Methods: Glucose homeostasis, insulin sensitivity, exercise capacity, and electron transport chain content/activity were examined in wildtype (WT) and AMPK β1β2 muscle-specific null (AMPK-MKO) mice fed a high-fat diet (HFD) with or without R419 supplementation. Results: There was no change in weight gain, adiposity, glucose tolerance or insulin sensitivity between HFD-fed WT and AMPK-MKO mice. In both HFD-fed WT and AMPK-MKO mice, R419 enhanced insulin tolerance, insulin-stimulated glucose disposal, skeletal muscle 2-deoxyglucose uptake, Akt phosphorylation and glucose transporter 4 (GLUT4) content independently of alterations in body mass. In WT, but not AMPK-MKO mice, R419 improved treadmill running capacity. Treatment with R419 increased muscle electron transport chain content and activity in WT mice; effects which were blunted in AMPK-MKO mice. Conclusions: Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity.

Keywordsexercise-mimetic; mitochondrial; diabetes; obesity; AMPK; complex-I; R419
Year2015
JournalMolecular Metabolism
Journal citation4 (9), pp. 643 - 651
PublisherElsevier B.V.
ISSN2212-8778
Digital Object Identifier (DOI)https://doi.org/10.1016/j.molmet.2015.06.002
Scopus EID2-s2.0-84940439443
Open accessOpen access
Page range643 - 651
Research GroupMary MacKillop Institute for Health Research
Publisher's version
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© 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Place of publicationNetherlands
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Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity
Annesley, Sarah J., Lay, Sui T., De Piazza, Shawn W., Sanislav, Oana, Hammersley, Eleanor, Allan, Claire Y., Francione, Lisa M., Bui, Minh Q., Chen, Zhi-Ping, Ngoei, Kevin R. W., Tassone, Flora, Kemp, Bruce E., Storey, Elsdon, Evans, Andrew, Loesch, Danuta Z. and Fisher, Paul R.. (2016). Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity. Disease Models and Mechanisms. 9(9), pp. 1295 - 1305. https://doi.org/10.1242/dmm.025684
Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson's Disease
Bayliss, Jacqueline A., Lemus, Moyra B., Stark, Romana, Santos, Vanessa V., Thompson, Aiysha, Rees, Daniel J., Galic, Sandra, Elsworth, John D., Kemp, Bruce Ernest, Davies, Jeffrey S. and Andrews, Zane B.. (2016). Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson's Disease. Journal of Neuroscience. 36(10), pp. 3049 - 3063. https://doi.org/10.1523/JNEUROSCI.4373-15.2016
Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression
Lally, James S. V., Ford, Rebecca J., Johar, Jasper, Crane, Justin D., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2015). Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression. Physiological Reports. 3(5), pp. 1 - 9. https://doi.org/10.14814/phy2.12343
Salicylate improves macrophage cholesterol homeostasis via activation of Ampk
Fullerton, Morgan D., Ford, Rebecca J., McGregor, Chelsea P., LeBlond, Nicholas D., Snider, Shayne A., Stypa, Stephanie A., Day, Emily A., Lhoták, Šárka, Schertzer, Jonathan D., Austin, Richard C., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2015). Salicylate improves macrophage cholesterol homeostasis via activation of Ampk. Journal of Lipid Research. 56(5), pp. 1025 - 1033. https://doi.org/10.1194/jlr.M058875
Choreography of AMPK activation
Langerdorf, Christopher G. and Kemp, Bruce Ernest. (2015). Choreography of AMPK activation. Cell Research. 25(1), pp. 5 - 6. https://doi.org/10.1038/cr.2014.163
Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise
O'Neill, Hayley M., Lally, James S., Galic, Sandra, Pulinilkunnil, Thomas, Ford, Rebecca J., Dyck, Jason R. B., Van Denderen, Bryce J,, Kemp, Bruce Ernest and Steinberg, Gregory R.. (2015). Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise. Physiological Reports. 3(7), pp. 1 - 10. https://doi.org/10.14814/phy2.12444
Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity
Ford, Rebecca, Fullerton, Morgan, Pinkosky, Stephen, Day, Emily, Scott, John, Oakhill, Jonathan, Bujak, Adam, Smith, Brennan, Crane, Justin, Blumer, Regje, Marcinko, Katarina, Kemp, Bruce, Gerstein, Hertzel and Steinberg, Gregory. (2015). Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochemical Journal. 468(1), pp. 125 - 132. https://doi.org/10.1042/BJ20150125
High intensity interval training improves liver and adipose tissue insulin sensitivity
Marcinko, Katarina, Sikkema, Sarah R., Samaan, M. Constantine, Kemp, Bruce Ernest, Fullerton, Morgan D. and Steinberg, Gregory R.. (2015). High intensity interval training improves liver and adipose tissue insulin sensitivity. Molecular Metabolism. 4(12), pp. 903 - 915. https://doi.org/10.1016/j.molmet.2015.09.006
Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release
Scott, John, Galic, Sandra, Graham, Kate, Foitzik, Richard, Ling, Naomi, Dite, Toby, Issa, Samah, Langendorf, Chris, Weng, Qing, Thomas, Helen, Kay, Thomas, Birnberg, Neal, Steinberg, Gregory, Kemp, Bruce and Oakhill, Jonathan. (2015). Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release. Chemistry and Biology. 22(6), pp. 705 - 711. https://doi.org/10.1016/j.chembiol.2015.05.011
AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism
Sung, Miranda M., Zordoky, Beshay N. M., Bujak, Adam L., Lally, James S. V., Fung, David, Young, Martin E., Horman, Sandrine, Miller, Edward J., Light, Peter E., Kemp, Bruce Ernest, Steinberg, Gregory R. and Dyck, Jason R. B.. (2015). AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism. Cardiovascular Research. 107(2), pp. 235 - 245. https://doi.org/10.1093/cvr/cvv166
Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis
O'Brien, Andrew J., Villani, Linda A., Broadfield, Lindsay A., Houde, Vanessa P., Galic, Sandra, Blandino, Giovanni, Kemp, Bruce Ernest, Tsakiridis, Theodoros, Muti, Paola and Steinberg, Gregory R.. (2015). Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis. Biochemical Journal. 469(2), pp. 177 - 187. https://doi.org/10.1042/Bj20150122
AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging
Bujak, Adam L., Crane, Justin D., Lally, James S., Ford, Rebecca J., Kang, Sally J., Rebalka, Irena A., Green, Alex E., Kemp, Bruce Ernest, Hawke, Thomas J., Schertzer, Jonathan D. and Steinberg, Gregory R.. (2015). AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell Metabolism. 21(6), pp. 883 - 890. https://doi.org/10.1016/j.cmet.2015.05.016
Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging
Crane, Justin D., MacNeil, Lauren G., Lally, James S. V., Ford, Rebecca J., Bujak, Adam L., Brar, Ikdip K., Kemp, Bruce Ernest, Raha, Sandeep, Steinberg, Gregory Robert and Tarnopolsky, Mark A.. (2015). Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging. Aging Cell. 14(4), pp. 625 - 634. https://doi.org/10.1111/acel.12341
Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder
Scott, John, Park, Elizabeth, Rodriguiz, Ramona, Oakhill, Jonathan, Issa, Samah, O'Brien, Matthew, Dite, Toby, Langendorf, Christopher, Wetsel, William, Means, Anthony and Kemp, Bruce. (2015). Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder. Scientific Reports. 5, pp. 1 - 10. https://doi.org/10.1038/srep14436
SnRK1 from Arabidopsis thaliana is an atypical AMPK
Emanuelle, Shane, Hossain, Mohammed Iqbal, Moller, Isabel E., Pedersen, Henriette L., van de Meene, Allison M. L., Doblin, Monika S., Koay, Ann, Oakhill, Jonathan S., Scott, John W., Willats, William G. T., Kemp, Bruce Ernest, Bacic, Antony, Gooley, Paul R. and Stapleton, David I.. (2015). SnRK1 from Arabidopsis thaliana is an atypical AMPK. Plant Journal. 82(2), pp. 183 - 192. https://doi.org/10.1111/tpj.12813
PPARδ Activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity
Bojic, Lazar, Telford, Dawn, Fullerton, Morgan, Ford, Rebecca, Sutherland, Brian, Edwards, Jane, Sawyez, Cynthia, Gros, Robert, Kemp, Bruce, Steinberg, Gregory and Huff, Murray. (2014). PPARδ Activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity. Journal of Lipid Research. 55(7), pp. 1254 - 1266. https://doi.org/10.1194/jlr.M046037
PPARδ activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity
Bojic, Lazar A., Telford, Dawn E., Fullerton, Morgan D., Ford, Rebecca J., Sutherland, Brian G., Edwards, Jane Y., Sawyez, Cynthia G., Gros, Robert, Kemp, Bruce Ernest, Steinberg, Gregory R. and Huff, Murray W.. (2014). PPARδ activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity. Journal of Lipid Research. 55(7), pp. 1254 - 1266. https://doi.org/10.1194/jlr.M046037
Muscle-specific AMPK ß1ß2-null mice display a myopathy due to loss of capillary density in nonpostural muscles
Thomas, Melissa, Wang, David, D'Souza, Donna, Krause, Matthew, Layne, Andrew, Criswell, David, O'Neill, Hayley, Connor, Michael, Anderson, Judy, Kemp, Bruce, Steinberg, Gregory and Hawke, Thomas. (2014). Muscle-specific AMPK ß1ß2-null mice display a myopathy due to loss of capillary density in nonpostural muscles. The FASEB Journal. 28(5), pp. 2098 - 2107. https://doi.org/10.1096/fj.13-238972
Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue
Wan, Zhongxiao, Root-Mccaig, Jared, Castellani, Laura, Kemp, Bruce, Steinberg, Gregory and Wright, David. (2014). Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue. Obesity: a resourch journal. 22(3), pp. 730 - 738. https://doi.org/10.1002/oby.20605
Activation of AMPK reduces the co-transporter activity of NKCC1
Fraser, Scott A., Davies, Matthew R. P., Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce Ernest and Power, David A.. (2014). Activation of AMPK reduces the co-transporter activity of NKCC1. Molecular Membrane Biology. 31(2-3), pp. 95 - 102. https://doi.org/10.3109/09687688.2014.902128
Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models
Perera, Nirma, Sheean, Rebecca, Scott, John, Kemp, Bruce, Horne, Malcolm and Turner, Bradley. (2014). Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models. PLoS One (online). 9(3), pp. 1 - 11. https://doi.org/10.1371/journal.pone.0090449
Reduced skeletal muscle AMPK and mitochondrial markers do not promote age-induced insulin resistance
Bujak, Adam, Blumer, Regje, Marcinko, Katarina, Fullerton, Morgan, Kemp, Bruce and Steinberg, Gregory. (2014). Reduced skeletal muscle AMPK and mitochondrial markers do not promote age-induced insulin resistance. Journal of Applied Physiology. 117(2), pp. 171 - 179. https://doi.org/10.1152/japplphysiol.01101.2013
Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress
McGee, Sean, Swinton, Courtney, Morrison, Shona, Gaur, Vidhi, Campbell, Duncan, Jorgensen, Sebastian, Kemp, Bruce, Baar, Keith, Steinberg, Gregory and Hargreaves, Mark. (2014). Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress. The FASEB Journal. 28(8), pp. 3384 - 3395. https://doi.org/10.1096/fj.14-249359
ATP sensitive bi-quinoline activator of the AMP-activated protein kinase
Scott, John, Oakhill, Jonathan, Ling, Naomi, Langendorf, Christopher, Foitzik, Richard, Kemp, Bruce and Issinger, Olaf-Georg. (2014). ATP sensitive bi-quinoline activator of the AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 443(2), pp. 435 - 440. https://doi.org/10.1016/j.bbrc.2013.11.130
The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies
Li, Li and Somerset, Shawn. (2014). The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies. Clinical Nutrition. 33(4), pp. 571 - 580. https://doi.org/10.1016/j.clnu.2014.04.004
Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662
Ducommun, Serge, Ford, Rebecca J., Bultot, Laurent, Deak, Maria, Bertrand, Luc, Kemp, Bruce Ernest, Steinberg, Gregory R. and Sakamoto, Kei. (2014). Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662. American Journal of Physiology - Endocrinology and Metabolism. 306(6), pp. 688 - 696. https://doi.org/10.1152/ajpendo.00672.2013
Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling
Scott, John, Ling, Naomi, Issa, Samah, Dite, Toby, O'Brien, Matthew, Chen, Zhi-Ping, Galic, Sandra, Langendorf, Christopher, Steinberg, Gregory, Kemp, Bruce and Oakhill, Jonathan. (2014). Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chemistry and Biology. 21(5), pp. 619 - 627. https://doi.org/10.1016/j.chembiol.2014.03.006
Novel mechanisms of Na+ retention in obesity: Phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK
Davies, Matthew R. P., Fraser, Scott A., Galic, Sandra, Choy, Suet-Wan, Katerelos, Marina, Gleich, Kurt, Kemp, Bruce Ernest, Mount, Peter F. and Power, David A.. (2014). Novel mechanisms of Na+ retention in obesity: Phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK. American Journal of Physiology - Renal Physiology. 307(1), pp. 96 - 106. https://doi.org/10.1152/ajprenal.00524.2013
Digestive system dysfunction in Cystic Fibrosis: Challenges for nutrition therapy
Li, Li and Somerset, Shawn. (2014). Digestive system dysfunction in Cystic Fibrosis: Challenges for nutrition therapy. Digestive and Liver Disease. 46(10), pp. 865 - 874. https://doi.org/10.1016/j.dld.2014.06.011
Mechanism of action of compound-13 : An a1-selective small molecule activator of AMPK
Hunter, Roger, Foretz, Marc, Bultot, Laurent, Fullerton, Morgan, Deak, Maria, Ross, Fiona, Hawley, Simon, Shpiro, Natalia, Viollet, Benoit, Barron, Denis, Kemp, Bruce, Steinberg, Gregory, Hardie, David Grahame and Sakamoto, Kei. (2014). Mechanism of action of compound-13 : An a1-selective small molecule activator of AMPK. Chemistry and Biology. 21(7), pp. 866 - 879. https://doi.org/10.1016/j.chembiol.2014.05.014
Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin
Fullerton, Morgan, Galic, Sandra, Marcinko, Katarina, Sikkema, Sarah, Pulinilkunnil, Thomas, Chen, Zhi-Ping, O'Neill, Hayley, Ford, Rebecca, Palanivel, Rengasamy, O'Brien, Matthew, Hardie, D. Grahame, Macaulay, Lance, Schertzer, Jonathan, Dyck, Jason, van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2013). Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nature Medicine. 19(12), pp. 1649 - 1654. https://doi.org/10.1038/nm.3372
AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice
O’Neill, Hayley M., Lally, James S., Galic, Sandra, Thomas, Melissa, Azizi, Paymon D., Fullerton, Morgan D., Smith, Brennan K., Pulinilkunnil, Thomas, Chen, Zhiping, Constantine Samaan, M., Jorgensen, Sebastian B., Dyck, Jason R. B., Holloway, Graham P., Hawke, Thomas J., van Denderen, Bryce J., Kemp, Bruce E. and Steinberg, Gregory R.. (2012). AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia. 57(8), pp. 1693 - 1702. https://doi.org/10.1007/s00125-014-3273-1
AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation
Zordoky, Beshay N.M., Nagendran, Jeevan, Pulinilkunnil, Thomas, Kienesberger, Petra C., Masson, Grant, Waller, Terri J., Kemp, Bruce E., Steinberg, Gregory R. and Dyck, Jason R. B.. (2012). AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation. Circulation Research. 115(5), pp. 518 - 524. https://doi.org/10.1161/CIRCRESAHA.115.304538
Chinese language reform in Singapore: teacher perceptions of instructional approaches and curriculum implementation
Li, Li, Zhao, Shouhui and Yeung, See. (2012). Chinese language reform in Singapore: teacher perceptions of instructional approaches and curriculum implementation. International Journal of Bilingual Education and Bilingualism. 15(5), pp. 533 - 548. https://doi.org/10.1080/13670050.2011.641938
The ancient drug salicylate directly activates AMP-activated protein kinase
Hawley, Simon, Fullerton, Morgan, Ross, Fiona, Schertzer, Jonathan, Chevtzoff, Cyrille, Walker, Katherine, Peggie, Mark, Zibrova, Darya, Green, Kevin, Mustard, Kirsty, Kemp, Bruce, Sakamoto, Kei, Steinberg, Gregory and Hardie, D. Grahame. (2012). The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 336(6083), pp. 918 - 922. https://doi.org/10.1126/science.1215327
Pro-GRP-derived peptides are expressed in colorectal cancer cells and tumors and are biologically active in vivo
Patel, Oneel, Clyde, Daniel, Chang, Mike, Nordlund, Marianne, Steel, Rohan, Kemp, Bruce, Pritchard, D. Mark, Shulkes, Arthur and Baldwin, Graham. (2012). Pro-GRP-derived peptides are expressed in colorectal cancer cells and tumors and are biologically active in vivo. Endocrinology. 153(3), pp. 1082 - 1092. https://doi.org/10.1210/en.2011-1875
The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-ß1 deficient mice
Mount, Peter, Gleich, Kurt, Tam, Shanna, Fraser, Scott, Choy, Suet-Wan, Dwyer, Karen, Lu, Bo, Van Denderen, Bryce, Fingerle-Rowson, Gunter, Bucala, Richard, Kemp, Bruce and Power, David. (2012). The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-ß1 deficient mice. PLoS One (online). 7(1), pp. 1 - 10. https://doi.org/10.1371/journal.pone.0029887
Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase
Alesultan, Ioana, Foller, Michael, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Zelenak, Christine, Frohlich, Henning, Velic, Ana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Volkl, Harald and Lang, Florian. (2011). Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase. Molecular Membrane Biology. 28(2), pp. 79 - 89. https://doi.org/10.3109/09687688.2010.520037
AMP-activated protein kinase (AMPK) ß1ß2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise
O'Neill, Hayley M., Maarbjerg, Stine J., Crane, Justin D., Jeppesen, Jacob, Jorgensen, Sebastian B., Schertzer, Jonathan D., Shyroka, Olga, Kiens, Bente, Van Denderen, Bryce J., Tarnopolsky, Mark A., Kemp, Bruce Ernest, Richter, Erik A. and Steinberg, Gregory R.. (2011). AMP-activated protein kinase (AMPK) ß1ß2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proceedings of the National Academy of Sciences of USA. 108(38), pp. 16092 - 16097. https://doi.org/10.1073/pnas.1105062108
Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation
Green, Michelle, Scott, John, Steel, Rohan, Oakhill, Jonathan, Kemp, Bruce and Means, Anthony. (2011). Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation. Journal of Biological Chemistry. 286(32), pp. 28066 - 28079. https://doi.org/10.1074/jbc.M111.251504
Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Galic, Sandra, Fullerton, Morgan, Schertzer, Jonathan, Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl, Izon, David, Honeyman, Jane, Chen, Zhi-Ping, Van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2011). Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577
Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Galic, Sandra, Fullerton, Morgan D., Schertzer, Jonathan D., Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl R., Izon, David, Honeyman, Jane, Chen, Zhi-Ping, van Denderen, Bryce J., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2011). Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577
Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase
Alesutan, Ioana, Munoz, Carlos, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Michael, Diana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Foller, Michael and Lang, Florian. (2011). Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 408(4), pp. 505 - 510. https://doi.org/10.1016/j.bbrc.2011.04.015
Inhibition of Connexin 26 by the AMP-activated protein kinase
Alesutan, Ioana, Sopjani, Mentor, Munoz, Carlos, Fraser, Scott, Kemp, Bruce, Foller, Michael and Lang, Florian. (2011). Inhibition of Connexin 26 by the AMP-activated protein kinase. Journal of Membrane Biology: an international journal for studies on the structure, function and genesis of biomembranes. 240(3), pp. 151 - 158. https://doi.org/10.1007/s00232-011-9353-y
AMPK is a direct adenylate charge-regulated protein kinase
Oakhill, Jonathan S., Steel, Rohan, Chen, Zhi-Ping, Scott, John W., Ling, Naomi, Tam, Shanna and Kemp, Bruce Ernest. (2011). AMPK is a direct adenylate charge-regulated protein kinase. Science. 332(6036), pp. 1433 - 1435. https://doi.org/10.1126/science.1200094
AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1
Fraser, Scott A., Choy, Suet-Wan, Pastor-Soler, Núria M., Li, Hui, Davies, Matthew R. P., Cook, Natasha, Katerelos, Marina, Mount, Peter F., Gleich, Kurt, McRae, Jennifer L., Dwyer, Karen M., van Denderen, Bryce J. W., Hallows, Kenneth R., Kemp, Bruce E. and Power, David A.. (2010). AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1. American Journal of Physiology - Renal Physiology. 305(5), pp. F679 - F690. https://doi.org/10.1152/ajprenal.00407.2012
Transcriptome-Wide Characterization of Gene Expression Associated with Unruptured Intracranial Aneurysms
Li, Li, Yang, Xinjian, Jiang, Fan, Dusting, Gregory and Wu, Zhongxue. (2009). Transcriptome-Wide Characterization of Gene Expression Associated with Unruptured Intracranial Aneurysms. European Neurology. 62(6), pp. 330 - 337. https://doi.org/10.1159/000236911
Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity
Lessard, Sarah J., Rivas, Donato A., Chen, Zhu-Ping, van Denderen, Bryce J., Watt, Matthew J., Koch, Lauren G., Britton, Steven L., Kemp, Bruce Ernest and Hawley, John Alan. (2009). Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity. Endocrinology. 150(11), pp. 4883 - 4891. https://doi.org/10.1210/en.2009-0158
Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans
Yeo, Wee Kian, Lessard, Sarah J., Chen, Zhi-Ping, Garnham, Andrew P., Burke, Louise, Rivas, Donato A., Kemp, Bruce Ernest and Hawley, John Alan. (2008). Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans. Journal of Applied Physiology. 105(5), pp. 1519 - 1526. https://doi.org/10.1152/japplphysiol.90540.2008
Activation of AMPK reduces the co-transporter activity of NKCC1
Fraser, Scott A., Davies, Matthew, Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce E. and Power, David A.. (1999). Activation of AMPK reduces the co-transporter activity of NKCC1. Molecular Membrane Biology. 31(2-3), pp. 95 - 102. https://doi.org/10.3109/09687688.2014.902128
Myosin light chain kinases
Kemp, Bruce E. and Stull, James T.. (1990). Myosin light chain kinases. In In B. E. Kemp (Ed.). Peptides and Protein Phosphorylation pp. 115 - 133 CRC Press. https://doi.org/10.1201/9781351075442