Cited by 238Metabolism, Diabetes, and CancerNatural Antidiabetic Agents StudiesAdipose Tissue and Metabolism

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

5′-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside

Open access

Jakobsen, Søren N., Hardie, D. Grahame, Morrice, Nick, Tornqvist, Hans E.·2001·Journal of Biological Chemistry

Open this paper in CoChat — free account Open PDF

Abstract

Exercise is known to increase insulin sensitivity and is an effective form of treatment for the hyperglycemia observed in type 2 diabetes. Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle. Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1). We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR. In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789. This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR. The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR. These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1074/jbc.c100483200

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A comprehensive set of sequence analysis programs for the VAX
Devereux, J., Haeberli, P. E., & Smithies, O. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.1part1.387 · Cited by 14,222
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574
The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307
Aguirre, V., Uchida, T., Yenush, L., Davis, R., & White, M. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.9047 · Cited by 1,487
[11] Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates
Boyle, W. J., van der Geer, P., & Hunter, T. R. (1991) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(91)01013-r · Cited by 1,421
The AMP‐Activated Protein Kinase: Fuel Gauge of the Mammalian Cell?
Hardie, D. G., & Carling, D. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00259.x · Cited by 1,317
Self-citation
Characterization of the AMP-activated Protein Kinase Kinase from Rat Liver and Identification of Threonine 172 as the Major Site at Which It Phosphorylates AMP-activated Protein Kinase
Hawley, S. A., Davison, M., Woods, A., Davies, S. P., Beri, R. K., Carling, D., & Hardie, D. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27879 · Cited by 1,264
Self-citation
5-Aminoimidazole-4-Carboxamide Ribonucleoside. A Specific Method for Activating AMP-Activated Protein Kinase in Intact Cells?
Corton, J. M., Gillespie, J. G., Hawley, S. A., & Hardie, D. G. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20498.x · Cited by 1,232
Self-citation
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling
SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K. (1998) · Biochemical Journal · doi:10.1042/bj3330471 · Cited by 953
A Role for AMP-Activated Protein Kinase in Contraction- and Hypoxia-Regulated Glucose Transport in Skeletal Muscle
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
Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport
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

Show all 36 references

Research works printed but not linked: 5

Ploug, 1987, Am. J. Physiol., 253, E12
Ploug, 1984, Am. J. Physiol., 247, E726
Winder, 1996, Am. J. Physiol., 270, E299
Merrill, 1997, Am. J. Physiol., 273, E1107
Hayashi, 1998, Diabetes, 47, 1369

Sorted by citations

Items 101–200 of 238

Activation of AMP‐activated protein kinase signaling pathway by adiponectin and insulin in mouse adipocytes: requirement of acyl‐CoA synthetases FATP1 and Acsl1 and association with an elevation in AMP/ATP ratio
Liu, Q., Gauthier, M., Sun, L., Ruderman, N. B., & Lodish, H. F. (2010) · The FASEB Journal · doi:10.1096/fj.10-159723 · Cited by 69
The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser358 in adipocytes
Henriksson, E., Jones, H. A., Patel, K., Peggie, M. W., Morrice, N. A., Sakamoto, K., & Göransson, O. (2012) · Biochemical Journal · doi:10.1042/bj20111932 · Cited by 69
Self-citation
Bioenergy sensing in the brain
Amato, S., & Man, H. (2011) · Cell Cycle · doi:10.4161/cc.10.20.17953 · Cited by 73
Interplay and Effects of Temporal Changes in the Phosphorylation State of Serine-302, -307, and -318 of Insulin Receptor Substrate-1 on Insulin Action in Skeletal Muscle Cells
Weigert, C., Kron, M., Kalbacher, H., Pohl, A. K., Runge, H., Häring, H., Schleicher, E. D., & Lehmann, R. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0102 · Cited by 68
Berberine improves mesenteric artery insulin sensitivity through up‐regulating insulin receptor‐mediated signalling in diabetic rats
Geng, F., Li, G., Zhang, X., Zhang, P., Dong, M., Zhao, Z., Zhang, Y., Dong, L., & Gao, F. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13466 · Cited by 68
Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases
Levkovitz, Y., Ben-shushan, G., Herschkovitz, A., Isaac, R., Gil‐Ad, I., Shvartsman, D. E., Ronen, D., Weizman, A., & Zick, Y. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.05.009 · Cited by 64
Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats
Nausheen, S., Shah, I. H., Pezeshki, A., Sigalet, D. L., & Chelikani, P. K. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00130.2013 · Cited by 61
Rat hindlimb unloading down-regulates insulin like growth factor-1 signaling and AMP-activated protein kinase, and leads to severe atrophy of the soleus muscle
Han, B., Zhu, M. J., Ma, C., & Du, ‬. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-102 · Cited by 63
Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism
Booth, A. D., Magnuson, A. M., Fouts, J. K., Wei, Y., Wang, D., Pagliassotti, M. J., & Foster, M. T. (2018) · Adipocyte · doi:10.1080/21623945.2018.1525252 · Cited by 61
Small Molecule Adenosine 5′-Monophosphate Activated Protein Kinase (AMPK) Modulators and Human Diseases
Rana, S., Blowers, E. C., & Natarajan, A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401994c · Cited by 63
Adenosine Monophosphate-activated Protein Kinase (AMPK) Activators For the Prevention, Treatment and Potential Reversal of Pathological Pain
Price, T. J., Das, V., & Dussor, G. O. (2016) · Current Drug Targets · doi:10.2174/1389450116666151102095046 · Cited by 60
AMPK activation inhibits the expression of HIF-1α induced by insulin and IGF-1
Treins, C., Murdaca, J., OBBERGHEN, E. V., & Giorgetti‐Peraldi, S. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.088 · Cited by 60
Chronic rosiglitazone treatment restores AMPKα2 activity in insulin-resistant rat skeletal muscle
Lessard, S. J., Chen, Z., Watt, M. J., Hashem, M., Reid, J. J., Febbraio, M. A., Kemp, B. E., & Hawley, J. A. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00096.2005 · Cited by 60
Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo
Longnus, S. L., Ségalen, C., Giudicelli, J., Sajan, M. P., Farese, R. V., & Van Obberghen, E. (2005) · Diabetologia · doi:10.1007/s00125-005-0016-3 · Cited by 58
“This dissociation between PI3-kinase and PKB is similar to that described in previous reports [18, 60].”
BackgroundResultInfluential
Murine Protein Serine/Threonine Kinase 38 Stimulates TGF-β Signaling in a Kinase-dependent Manner via Direct Phosphorylation of Smad Proteins
Seong, H., Jung, H., & Ha, H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.138370 · Cited by 58
Role and mechanism of the AMPK pathway in waterborne Zn exposure influencing the hepatic energy metabolism of Synechogobius hasta
Wu, K., Huang, C., Shi, X., Chen, F., Xu, Y., Pan, Y., Luo, Z., & Liu, X. (2016) · Scientific Reports · doi:10.1038/srep38716 · Cited by 57
Chapter 13 Phosphorylation of IRS Proteins
Sun, X., & Liu, F. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00613-4 · Cited by 57
Targeting AMPK for the Alleviation of Pathological Pain
Asiedu, M. N., Dussor, G. O., & Price, T. J. (2016) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-319-43589-3_11 · Cited by 56
“Using AMPK activators as a possible alternative approach to circumvent this problem is attractive from a molecular signaling standpoint because AMPK activation negatively influences both the mTORC1 and MAPK signaling pathways and attenuates feedback signaling mechanisms (Jakobsen et al. 2001).”
Background
Interleukin-6 Attenuates Insulin-Mediated Increases in Endothelial Cell Signaling but Augments Skeletal Muscle Insulin Action via Differential Effects on Tumor Necrosis Factor-α Expression
Yuen, D. Y. C., Dwyer, R. M., Matthews, V. B., Zhang, L., Drew, B. G., Neill, B., Kingwell, B. A., Clark, M. G., Rattigan, S., & Febbraio, M. A. (2009) · Diabetes · doi:10.2337/db08-0775 · Cited by 55
The apelin/APJ system as a therapeutic target in metabolic diseases
Castan‐Laurell, I., Masri, B., & Valet, P. (2018) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1561871 · Cited by 56
“Apelin-induced activation of AMPK in different tissues has strengthened its therapeutic potential.”
BackgroundInfluential
Down-Regulation of Growth Signaling Pathways Linked to a Reduced Cotyledonary Vascularity in Placentomes of Over-Nourished, Obese Pregnant Ewes
Zhu, M. J., Du, M., Nijland, M. J., Nathanielsz, P. W., Hess, B. W., Moss, G. E., & Ford, S. P. (2009) · Placenta · doi:10.1016/j.placenta.2009.02.001 · Cited by 54
Involvement of the AMPK–PTEN pathway in insulin resistance induced by high glucose in cultured rat podocytes
Rogacka, D., Piwkowska, A., Audzeyenka, I., Angielski, S., & Jankowski, M. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.04.008 · Cited by 54
In vitro experimental models for examining the skeletal muscle cell biology of exercise: the possibilities, challenges and future developments
Carter, S., & Solomon, T. P. J. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2210-4 · Cited by 58
Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: Comparison to parathyroid hormone and insulin
Schnoke, M., & Midura, R. J. (2007) · Journal of Orthopaedic Research® · doi:10.1002/jor.20373 · Cited by 53
Skeletal muscle insulin resistance: the interplay of local lipid excess and mitochondrial dysfunction
Chow, L. S., From, A. H. L., & Seaquist, E. R. (2009) · Metabolism · doi:10.1016/j.metabol.2009.07.009 · Cited by 54
“Enhanced glucose uptake from contraction appears to be due to increased GLUT4 translocation due to several mediators: activation of myocyte enhancer factor–2 [36,37,40], activation of a Rab GTPase-activating protein (AS160) [41-43], and improved insulin signaling [44], possibly through the tuberous sclerosis complex […”
Background
SIK2 Can be Activated by Deprivation of Nutrition and It Inhibits Expression of Lipogenic Genes in Adipocytes
Du, J., Qiu, C., Takemori, H., & Xu, H. (2008) · Obesity · doi:10.1038/oby.2007.98 · Cited by 51
“Phosphorylation of this residue by AMPK results in increased activity of PI3 kinase in C2C12 cells (18).”
Background
A modelling–experimental approach reveals insulin receptor substrate (IRS)‐dependent regulation of adenosine monosphosphate‐dependent kinase (AMPK) by insulin
Sonntag, A., Pezze, P. D., Shanley, D. P., & Thedieck, K. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08582.x · Cited by 50
Cytokine Regulation of AMPK signalling
Steinberg, G. R. (2009) · Frontiers in bioscience · doi:10.2741/3350 · Cited by 49
The Phosphorylation of Ser318 of Insulin Receptor Substrate 1 Is Not per se Inhibitory in Skeletal Muscle Cells but Is Necessary to Trigger the Attenuation of the Insulin-stimulated Signal
Weigert, C., Hennige, A. M., Brischmann, T., Beck, A., Moeschel, K., Schaüble, M., Brodbeck, K., Häring, H.-U., Schleicher, E. D., & Lehmann, R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506134200 · Cited by 50
Murine Protein Serine-threonine Kinase 38 Activates p53 Function through Ser15 Phosphorylation
Seong, H., & Ha, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.347757 · Cited by 48
Links between Insulin Resistance and Periodontal Bacteria: Insights on Molecular Players and Therapeutic Potential of Polyphenols
Thouvenot, K., Turpin, T., Taïlé, J., Clément, K., Meilhac, O., & Gonthier, M. (2022) · Biomolecules · doi:10.3390/biom12030378 · Cited by 51
“Many of these kinases are activated along insulin-unrelated pathways, as in the case of the inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ), c-Jun NH2-terminal kinase (JNK) [38] and AMP-activated protein kinase (AMPK) [39].”
Background
Chapter 12 Serine Kinases of Insulin Receptor Substrate Proteins
Boura‐Halfon, S., & Zick, Y. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00612-2 · Cited by 53
Role of AMP-activated protein kinase on cardio-metabolic abnormalities in the development of diabetic cardiomyopathy: A molecular landscape
Haye, A., Ansari, M. A., Rahman, S. O., Shamsi, Y., Ahmed, D., & Sharma, M. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173376 · Cited by 47
AMP-activated protein kinase is negatively associated with intramuscular fat content in longissimus dorsi muscle of beef cattle
Underwood, K. R., Means, W. J., Zhu, M., Ford, S. P., Hess, B. W., & Du, ‬. (2007) · Meat Science · doi:10.1016/j.meatsci.2007.10.025 · Cited by 45
“However, the recent report that AMPK facilitates insulin/IGF-1 signaling through phosphorylation of insulin receptor substrate-1 (IRS-1) may provide explanation for this controversy (Jakobsen et al., 2001; Du et al., 2007).”
Background
Meiotic Induction by Heat Stress in Mouse Oocytes: Involvement of AMP-Activated Protein Kinase and MAPK Family Members
LaRosa, C., & Downs, S. M. (2006) · Biology of Reproduction · doi:10.1095/biolreprod.106.057422 · Cited by 44
“Moreover, the activation of MAPK14 and MAPK8/9 has been associated with the activation of PRKA [69–75].”
Background
Glimepiride enhances intrinsic peroxisome proliferator-activated receptor-γ activity in 3T3-L1 adipocytes
Inukai, K., Watanabe, M., Nakashima, Y., Takata, N., Isoyama, A., Sawa, T., Kurihara, S., Awata, T., & Katayama, S. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.12.190 · Cited by 44
Caffeine modulates phosphorylation of insulin receptor substrate-1 and impairs insulin signal transduction in rat skeletal muscle
Egawa, T., Tsuda, S., Ma, X., Hamada, T., & Hayashi, T. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00249.2011 · Cited by 46
“Ser(789) of IRS-1 has been shown to be phosphorylated in vitro by AMPK and to promote insulin signaling in muscle C2C12 cells (25).”
Background
Branched chain amino acids and metabolic regulation
Wang, C., & Guo, F. (2013) · Chinese Science Bulletin · doi:10.1007/s11434-013-5681-x · Cited by 43
High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δAgonism
Benetti, E., Mastrocola, R., Rogazzo, M., Chiazza, F., Aragno, M., Fantozzi, R., Collino, M., & Minetto, M. A. (2013) · Mediators of Inflammation · doi:10.1155/2013/509502 · Cited by 44
Genistein promotes insulin action through adenosine monophosphate–activated protein kinase activation and p70 ribosomal protein S6 kinase 1 inhibition in the skeletal muscle of mice fed a high energy diet
Elumalai, A., & Anuradha, C. V. (2012) · Nutrition Research · doi:10.1016/j.nutres.2012.06.002 · Cited by 41
Exercise improves phosphatidylinositol‐3,4,5‐trisphosphate responsiveness of atypical protein kinase C and interacts with insulin signalling to peptide elongation in human skeletal muscle
Frøsig, C., Sajan, M. P., Maarbjerg, S., Brandt, N., Roepstorff, C., Wojtaszewski, J. F. P., Kiens, B., Farese, R. V., & Richter, E. A. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.136614 · Cited by 44
“A number of kinases including PKB, c-Jun NH2 kinase, AMPK and aPKC (Aronson et al. 1998; Fujii et al. 2000; Jakobsen et al. 2001; Sakamoto et al. 2002; Moeschel et al. 2004; Weigert et al. 2005) have these characteristics; however, most research so far has evaluated regulation in regard to IRS-1.”
Background
Phospholipase D1 Mediates AMP-Activated Protein Kinase Signaling for Glucose Uptake
Kim, J. H., Park, J.-M., Yea, K., Kim, H. W., Suh, P., & Ryu, S. H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009600 · Cited by 42
“Activation of AMPK by AICAR has also been shown to increase glucose uptake via a phosphoinositide-3 kinase (PI-3K)-independent mechanism [14].”
Background
Nuclear Forkhead Box O1 Controls and Integrates Key Signaling Pathways in Hepatocytes
Naïmi, M., Gautier, N., Chaussade, C., Valverde, Á. M., Accili, D., & OBBERGHEN, E. V. (2007) · Endocrinology · doi:10.1210/en.2006-1411 · Cited by 42
Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice
Tong, J. F., Yan, X., Jx, Z., Zhu, M. J., Nathanielsz, P. W., & Du, ‬. (2011) · Nutrition and Diabetes · doi:10.1038/nutd.2011.3 · Cited by 41
“14 Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a master controller of energy metabolism in SM. 22,23 AMPK controls SM development by enhancing the insulin signaling pathway 24 and inhibiting adipogenesis, 10,25,26 both of which link to SM insulin resistance.”
Influential
Effects of contraction and insulin on protein synthesis, AMP-activated protein kinase and phosphorylation state of translation factors in rat skeletal muscle
Miranda, L., Horman, S., Potter, I. D., Hue, L., Jensen, J., & Rider, M. H. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0368-2 · Cited by 40
“AMPK activation by AICAR has been shown to increase insulin receptor substrate-1 (IRS-1) phosphorylation in C2C12 myotubes, and this correlated with an increase in IRS-1-associated PI 3-kinase activity [ 22 ].”
Background
SIRT1-AMPK crosstalk is involved in high glucose-dependent impairment of insulin responsiveness in primary rat podocytes
Rogacka, D., Piwkowska, A., Audzeyenka, I., Angielski, S., & Jankowski, M. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.11.005 · Cited by 39
In vivo, ex vivo, and in vitro studies on apelin's effect on myocardial glucose uptake
Xu, S., Han, P., Huang, M., Wu, J. C., Chang, C.-P., Tsao, P. S., & Yue, P. (2012) · Peptides · doi:10.1016/j.peptides.2012.08.004 · Cited by 40
Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles
Martino, A. D., Kucharczyk, P., Capáková, Z., Humpolíček, P., & Sedlařík, V. (2017) · Journal of Nanoparticle Research · doi:10.1007/s11051-017-3756-3 · Cited by 36
“6c, in particular 4, 5, and 6, could relate to products resulting from the MTIC degradation of MTIC in AIC, as reported in previous studies (Jakobsen et al. 2001; Fiore et al. 1985).”
Result
AICAR and hyperosmotic stress increase insulin-stimulated glucose transport
Smith, J. L., Patil, P. B., & Fisher, J. S. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01297.2004 · Cited by 36
Voluntary exercise increases adult hippocampal neurogenesis by increasing GSK-3β activity in mice
Zang, J., Liu, Y., Li, W., Xiao, D., Zhang, Y., Luo, Y., Liang, W., Liu, F., & Wei, W. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.04.024 · Cited by 35
Repeated Application of Low-Frequency Electroacupuncture Improves High-Fructose Diet-Induced Insulin Resistance in Rats
Tominaga, A., ISHIZAKI, N., Naruse, Y., Kitakoji, H., & Yamamura, Y. (2011) · Acupuncture in Medicine · doi:10.1136/acupmed-2011-010006 · Cited by 34
Effects of thyroid state on AMP-activated protein kinase and acetyl-CoA carboxylase expression in muscle
Park, S. H., Paulsen, S. R., Gammon, S. R., Mustard, K. J., Hardie, D. G., & Winder, W. W. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00504.2002 · Cited by 33
Self-citation
Inhibition of Insulin-Stimulated Glycogen Synthesis by 5-Aminoimidasole-4-Carboxamide-1-β-d-Ribofuranoside-Induced Adenosine 5′-Monophosphate-Activated Protein Kinase Activation: Interactions with Akt, Glycogen Synthase Kinase 3-3α/β, and Glycogen Synthase in Isolated Rat Soleus Muscle
Fediuc, S., Gaidhu, M. P., & Ceddia, R. B. (2006) · Endocrinology · doi:10.1210/en.2006-0480 · Cited by 33
Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance
Louden, E. D., Chi, M. M.-Y., & Moley, K. H. (2008) · Reproduction · doi:10.1530/rep-08-0161 · Cited by 31
“IGF-1R gene ( Jakobsen, et al. 2001; Raile, et al. 2005).”
Background
Autophagic degradation of the androgen receptor mediated by increased phosphorylation of p62 suppresses apoptosis in hypoxia
Mitani, T., Minami, M., Harada, N., Ashida, H., & Yamaji, R. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.07.009 · Cited by 31
4-Hydroxyisoleucine improves insulin resistance by promoting mitochondrial biogenesis and act through AMPK and Akt dependent pathway
Rawat, A. K., Korthikunta, V., Gautam, S., Pal, S., Narender, T., Tamrakar, A. K., & Srivastava, R. (2014) · Fitoterapia · doi:10.1016/j.fitote.2014.10.006 · Cited by 29
“It may have an important role in the increase of glucose uptake in response to AMPK activation [34,35].”
Background
Potential Role of the AMP-activated Protein Kinase in Regulation of Insulin Action.
Fisher, J. S. (2006) · PubMed · Cited by 30
Naturally occurring R225W mutation of the gene encoding AMP-activated protein kinase (AMPK)γ3 results in increased oxidative capacity and glucose uptake in human primary myotubes
Crawford, 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
“While the mechanisms underlying the AMPK-mediated increases in glucose uptake have not been fully elucidated, AMPK has been shown to phosphorylate and activate TBC1 domain family, member 4 (TBC1D4) and the IRS-1, both of which stimulate GLUT4 translocation [30, 31].”
Background
In Vitro Phosphorylation of Insulin Receptor Substrate 1 by Protein Kinase C-ζ: Functional Analysis and Identification of Novel Phosphorylation Sites
Sommerfeld, M. R., Metzger, S. U., Stosik, M., Tennagels, N., & Eckel, J. (2004) · Biochemistry · doi:10.1021/bi049640v · Cited by 30
Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells
Chen, X., Zhao, X., Lan, F., Zhou, T., Cai, H. “., Sun, H., Kong, W., & Kong, W. (2017) · Scientific Reports · doi:10.1038/s41598-017-13251-0 · Cited by 30
Zinc finger protein ZPR9 functions as an activator of AMPK-related serine/threonine kinase MPK38/MELK involved in ASK1/TGF-β/p53 signaling pathways
Seong, H., Manoharan, R., & Ha, H. (2017) · Scientific Reports · doi:10.1038/srep42502 · Cited by 28
Adenosine Monophosphate-Activated Protein Kinase Activation, Substrate Transporter Translocation, and Metabolism in the Contracting Hyperthyroid Rat Heart
Heather, L. C., Cole, M. A., Atherton, H. J., Coumans, W. A., Evans, R. D., Tyler, D. J., Glatz, J. F. C., Luiken, J. J. F. P., & Clarke, K. (2009) · Endocrinology · doi:10.1210/en.2009-0593 · Cited by 27
Stress hyperglycemia and enhanced sensitivity to myocardial infarction
Webster, K. A. (2008) · Current Hypertension Reports · doi:10.1007/s11906-008-0015-0 · Cited by 28
Mechanism of feedback regulation of insulin receptor substrate-1 phosphorylation in primary adipocytes
Hers, I., & Tavaré, J. M. (2005) · Biochemical Journal · doi:10.1042/bj20041531 · Cited by 27
AMP‐activated protein kinase activation in skeletal muscle modulates exercise‐induced uncoupled protein 1 expression in brown adipocyte in mouse model
Kim, H. J., Kim, Y. J., & Seong, J. K. (2022) · The Journal of Physiology · doi:10.1113/jp282999 · Cited by 31
“…conditioned medium (CM) of the C2C12 myotubes with an AMPK agonist (AICAR; 5-aminoimidazole-4-carboxamide ribonucleotide), which is widely used to mimic the condition of aerobic exercise (Iglesias et al., 2002; Jakobsen et al., 2001; Sanchez et al., 2013), and incubated the brown adipocytes in it.”
BackgroundMethod
TG accumulation inhibitory effects of Jinqi formula by AMPK signaling pathway
Qian, Q., Liu, X., He, W., An, Y., Chen, Q., Wu, J., Deng, Y., Guo, L., Zhang, Y., & Wang, T. (2012) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2012.05.052 · Cited by 25
PDK1 Protein Phosphorylation at Thr354 by Murine Protein Serine-Threonine Kinase 38 Contributes to Negative Regulation of PDK1 Protein Activity
Seong, H., Jung, H., Manoharan, R., & Ha, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.331827 · Cited by 25
Deficiency of Phosphoinositide 3-Kinase Enhancer Protects Mice From Diet-Induced Obesity and Insulin Resistance
Chan, C. B., Liu, X., Jung, D. Y., Jun, J. Y., Luo, H. R., Kim, J. K., & Ye, K. (2010) · Diabetes · doi:10.2337/db09-1404 · Cited by 25
Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
Rajan, M. R., Fagerholm, S., Jönsson, C., Kjølhede, P., Turkina, M. V., & Strålfors, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059725 · Cited by 24
A crucial role for the phosphorylation of STRAP at Ser188by MPK38 in STRAP-dependent cell death through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways
Seong, H., Manoharan, R., & Ha, H. (2014) · Cell Cycle · doi:10.4161/15384101.2014.952165 · Cited by 24
Exendin-4 and exercise improve hepatic glucose homeostasis by promoting insulin signaling in diabetic rats
Park, S., Hong, S. M., & Ahn, I. S. (2009) · Metabolism · doi:10.1016/j.metabol.2009.06.026 · Cited by 23
“In addition, serine phosphorylation of AMPK, an energy sensor that is known to stimulate fatty acid oxidation by regulating acetyl coenzyme A carboxylase activity [26,27], was stimulated in the exendin-4 and exercise groups of diabetic rats (Fig.”
Background
Metabolic and transcriptome responses of RNAi-mediated AMPKα knockdown in Tribolium castaneum
Jiang, H., Zhang, N., Ji, C., Meng, X., Qian, K., Zheng, Y., & Wang, J. (2020) · BMC Genomics · doi:10.1186/s12864-020-07070-3 · Cited by 23
Exogenous Nucleotides Ameliorate Insulin Resistance Induced by Palmitic Acid in HepG2 Cells through the IRS-1/AKT/FOXO1 Pathways
Song, L., Li, Y., & Xu, M. (2024) · Nutrients · doi:10.3390/nu16121801 · Cited by 21
“The results are shown in Figure 3g–i.”
Melatonin‐mediated insulin synthesis during endoplasmic reticulum stress involves HuD expression in rat insulinoma INS ‐1E cells
Yoo, Y. (2013) · Journal of Pineal Research · doi:10.1111/jpi.12064 · Cited by 20
Oxygen Tension Regulates the Stability of Insulin Receptor Substrate-1 (IRS-1) through Caspase-mediated Cleavage
Kang, S. G., Brown, A. L., & Chung, J. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m610659200 · Cited by 19
δ-Opioid Receptors Stimulate the Metabolic Sensor AMP-Activated Protein Kinase through Coincident Signaling with Gq/11-Coupled Receptors
Olianas, M. C., Dedoni, S., Olianas, A., & Onali, P. (2011) · Molecular Pharmacology · doi:10.1124/mol.111.075267 · Cited by 19
“There is evidence for the occurrence in different cell types of a crosstalk between AMPK and insulin receptor signaling (Towler and Hardie, 2007), and it has been reported that AMPK may regulate PI3K activity (Jakobsen et al., 2001; Tao et al., 2010).”
Background
Thr55 phosphorylation of p21 by MPK38/MELK ameliorates defects in glucose, lipid, and energy metabolism in diet-induced obese mice
Seong, H., & Ha, H. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1616-z · Cited by 20
The combined role of allelic variants of IRS-1 and IRS-2 genes in susceptibility to type2 diabetes in the Punjabi Pakistani subjects
Ijaz, A., Babar, S., Sarwar, S., Shahid, S. U., & Shabana, S. (2019) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-019-0459-1 · Cited by 23
Identification of Phosphorylation Sites in Insulin Receptor Substrate-1 by Hypothesis-Driven High-Performance Liquid Chromatography−Electrospray Ionization Tandem Mass Spectrometry
Yi, Z., Luo, M., Carroll, C. A., Weintraub, S. T., & Mandarino, L. J. (2005) · Analytical Chemistry · doi:10.1021/ac050760y · Cited by 19
Combination Treatment of Deep Sea Water and Fucoidan Attenuates High Glucose-Induced Insulin-Resistance in HepG2 Hepatocytes
He, S., Peng, W.-B., & Zhou, H. (2018) · Marine Drugs · doi:10.3390/md16020048 · Cited by 17
“Moreover, previous research elucidated that activated AMPK rapidly phosphorylated IRS-1 on Ser789, which led to an increase in insulin-stimulated IRS-1-associated PI3K activity [6].”
Background
Associations between Acute and Chronic Effects of Exercise on Indicators of Metabolic Health: A Pilot Training Trial
Hecksteden, A., Grütters, T., & Meyer, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081181 · Cited by 20
Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells
Kamga-Simo, F. D. Y., Kamatou, G., Ssemakalu, C. C., & Shai, L. J. (2021) · Journal of Evidence-Based Integrative Medicine · doi:10.1177/2515690x211006333 · Cited by 16
Metabolic regulation by salt inducible kinases
Berdeaux, R. (2011) · Frontiers in Biology · doi:10.1007/s11515-011-1148-0 · Cited by 15
“The SIKs are members of the AMP-dependent protein kinase (AMPK)- related family of 14 serine/threonine kinases (Bright et al., 2009).”
Influential
Targeting AMPK for Therapeutic Intervention in Type 2 Diabetes
Kodiha, M., & Stochaj, U. (2011) · InTech eBooks · doi:10.5772/20930 · Cited by 14
“…et al. 1989; ; Watt et al., 2006 IRS1; adaptor protein Insulin receptor substrate 1, adaptor protein modulation of PI3 kinase signaling cytoplasm Jakobsen et al., 2001; Tzatsos & Tsichlis, 2007 KCNMA1 iso4; ┙ subunit of BKCa channel Potassium channel, activated in response to mem- brane…”
Background
Sodium oxamate reduces lactate production to improve the glucose homeostasis of Micropterus salmoides fed high-carbohydrate diets
Shen, H.-C., Chen, Z., Liu, X., Guan, J.-F., Xie, D., Li, Y., & Xu, C. (2022) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00226.2022 · Cited by 14
Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats
Duan, H., Song, S., Li, R., Hu, S., Zhuang, S., Liu, S., Li, X., & Gao, W. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01432-7 · Cited by 16
“Moreover, targeting AMPK signaling also improves insulin sensitivity, thereby addressing one of the central pathological features of MAFLD [40].”
Background
Chlorpromazine exacerbates hepatic insulin sensitivity via attenuating insulin and leptin signaling pathway, while exercise partially reverses the adverse effects
Park, S., Hong, S. M., Lee, J. E., & Sung, S. R. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.04.001 · Cited by 17
Multiple AMPK activators inhibit l -carnitine uptake in C2C12 skeletal muscle myotubes
Shaw, A., Jeromson, S., Watterson, K. R., Pediani, J. D., Gallagher, I. J., Whalley, T., Dreczkowski, G., Brooks, N. E., Galloway, S. D. R., & Hamilton, D. L. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00026.2016 · Cited by 13
“1 M for insulin stimulation) at 80 Ci/ Mol] and each treatment was completed with the addition of insulin (100 nM and 150 nM) or one of the following AMPK activators: AICAR [250 M (previously shown to activate AMPK at 500 M) (23)], 2,4-dinitrophenol (DNP) [500 M (activates AMPK in L6 myotubes at 500 M) (39)],”
Background
Effects of metformin on insulin resistance and metabolic disorders in tumor-bearing rats with advanced cachexia
Silva, F. D. F., Ortiz‐Silva, M., Galia, W. B. D. S., Cassolla, P., da Silva, F. G., Graciano, M. F. R., Carpinelli, Â. R., & de Souza, H. M. (2018) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2017-0171 · Cited by 13
“Once activated, AMPK stimulates the INS signaling pathway proteins, such as protein kinase 3 (PI3K) and protein kinase B (Akt or PKB) (Kurth-Kraczek et al. 1999; Jakobsen et al. 2001).”
Background
The Mechanisms of Insulin Action
White, M. F., & Copps, K. D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00033-0 · Cited by 12
Remodeling glucose and lipid metabolism through AMPK activation: relevance for treating obesity and Type 2 diabetes
Gaidhu, M. P., & Ceddia, R. B. (2009) · Clinical Lipidology · doi:10.2217/clp.09.30 · Cited by 12
The association of phosphoinositide 3‐kinase enhancer A with hepatic insulin receptor enhances its kinase activity
Chan, C. B., Liu, X., He, K., Qi, Q., Jung, D. Y., Kim, J. K., & Ye, K. (2011) · EMBO Reports · doi:10.1038/embor.2011.108 · Cited by 12
“Antibodies used in the western blot analysis were obtained from Santa Cruz Biotechnology (p110a, IRS1 and Akt) and Cell Signaling Technology (phospho-Akt and phospho-insulin-receptor, phospho-AMPK, phospho-ACC, phosphoFoxO1 and FoxO1).”
BackgroundInfluential
IGF-1 and Insulin Receptor Signalling in Insulin-Secreting Cells: From Function to Survival
Ullrich, S. (2013) · Springer eBooks · doi:10.1007/978-94-007-6686-0_26 · Cited by 12
The metabolic actions of thyroid hormone and leptin: a mandatory interplay or not?
Vettor, R. (2005) · Diabetologia · doi:10.1007/s00125-005-1703-9 · Cited by 11
“Early activation of AMPK occurs by leptin acting directly on muscle, whereas later activation depends on leptin functioning through the hypothalamic–sympathetic nervous system axis.”
BackgroundInfluential
Combination of mTOR inhibitor PP242 and AMPK activator metformin exerts enhanced inhibitory effects on colorectal carcinoma cells in vitro by blocking multiple kinase pathways
Sun, C., Yang, X., Jin, Z., & Gao, Z. (2022) · Journal of Chemotherapy · doi:10.1080/1120009x.2022.2091122 · Cited by 10
Higher Intake of Total Dietary Essential Amino Acids Is Associated with a Lower Prevalence of Metabolic Syndrome among Korean Adults
Im, J., Park, H., & Park, K. (2022) · Nutrients · doi:10.3390/nu14224771 · Cited by 8
“AMPK is an important cellular energy sensor and signal transducer for maintaining energy homeostasis, a process regulated by extensive metabolic stress [35,36] and which plays a role in regulating insulin sensitivity by directly phosphorylating insulin receptor substrate 1 [37] or by phosphorylating tuberous sclerosis…”
Background
AMPK signaling in neuronal polarization
Amato, S., & Man, H. (2012) · Communicative & Integrative Biology · doi:10.4161/cib.18968 · Cited by 9
Futsal and Continuous Exercise Induce Similar Changes in Specific Skeletal Muscle Signalling Proteins
Serpiello, F. R., McKenna, M. J., Coratella, G., Markworth, J. F., Tarperi, C., Bishop, D. J., Stepto, N. K., Cameron‐Smith, D., & Schena, F. F. (2014) · International Journal of Sports Medicine · doi:10.1055/s-0034-1367045 · Cited by 7
Regulation of glucose-dependent insulin secretion by insulin: Possible role of AMP-activated protein kinase
Park, S.-H., Kim, S.-Y., Baek, W., Lim, B., Park, J., Sung, H., Kim, Y., Bae, K., Bae, J., & Song, D. (2009) · Life Sciences · doi:10.1016/j.lfs.2009.05.010 · Cited by 7
Signaling by AMP‐activated Protein Kinase
Neumann, D., Wallimann, T., Rider, M. H., Tokarska-Schlattner, M., Hardie, D. G., & Schlattner, U. (2007) · Wiley eBooks · doi:10.1002/9783527621095.ch9 · Cited by 7
Self-citation

Authors: Jakobsen, S. N., Hardie, D. G., Morrice, N., & Tornqvist, H. E.
Affiliations: Novo Nordisk (Denmark) (DK)
Wellcome Trust (GB)
University of Dundee (GB)
Corresponding author: Jakobsen, Søren N.
ORCID: Jakobsen, Søren N.
Hardie, D. Grahame
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2001-12
Volume: 276
Issue: 50
Pages: 46912-46916
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.c100483200
OpenAlex: W2041502315
Cited by: 238
References: 36
Citations by year: 2025: 1 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 11 · 2013: 16 · 2012: 13
FWCI: 3.03
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6878 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Keywords: AMPK, IRS-1, AICAR, phosphatidylinositol 3-kinase, insulin signaling, skeletal muscle, C2C12 myotubes, physical activity, insulin sensitivity, type 2 diabetes, glucose transport
MeSH terms: Aminoimidazole Carboxamide, Animals, Binding Sites, Biological Transport, Cells, Cultured, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Glucose, Humans, Insulin, Multienzyme Complexes, Myocardium, Peptides, Phosphoproteins, Phosphorylation, Protein Binding, Recombinant Proteins, Ribonucleosides, Serine, Subcellular Fractions, Time Factors, Blotting, Western, Signal Transduction, Protein Serine-Threonine Kinases, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Mice, AMP-Activated Protein Kinases, Insulin Receptor Substrate Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

5′-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks