A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle

Glynn, Erin L.; Lujan, Heidi L.; Kramer, Victoria J.; Drummond, Micah J.; DiCarlo, Stephen E.; Rasmussen, Blake B.

doi:10.1139/h07-149

Cited by 45Metabolism, Diabetes, and CancerMuscle metabolism and nutritionPI3K/AKT/mTOR signaling in cancer

A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle

Open access

Glynn, Erin L., Lujan, Heidi L., Kramer, Victoria J., Drummond, Micah J., DiCarlo, Stephen E., Rasmussen, Blake B.·2008·Applied Physiology, Nutrition, and Metabolism

DOI 10.1139/h07-149PMC PMC2706125

Open this paper in CoChat — free account

Abstract

A chronic increase in physical activity and (or) endurance training can improve insulin sensitivity in insulin-resistant skeletal muscle. Cellular mechanisms responsible for the development of insulin resistance are unclear, though one proposed mechanism is that nutrient overload chronically increases available energy, over-activating the mammalian target of rapamycin (mTOR) and ribosomal S6 kinase 1 (S6K1) signaling pathway leading to increased phosphorylation of serine residues on insulin receptor substrate-1 (IRS-1). The objective of this study was to determine if increased physical activity would inhibit mTOR/S6K1 signaling and reduce IRS-1 serine phosphorylation in rat skeletal muscle. Soleus muscle was collected from fed male Sprague–Dawley sedentary rats (Inactive) and rats with free access to running wheels for 9 weeks (Active). Immunoblotting methods were used to measure phosphorylation status of mTOR, S6K1, IRS-1, and PKB/Akt (protein kinase B/AKT), and total abundance of proteins associated with the mTOR pathway. Muscle citrate synthase activity and plasma insulin and glucose concentrations were measured. Phosphorylation of mTOR (Ser 2448), S6K1 (Thr 389), and IRS-1 (Ser 636–639) was reduced in Active rats (p < 0.05). Total protein abundance of mTOR, S6K1, IRS-1, 4E-BP1, eEF2, PKB/Akt and AMPKα, and phosphorylation of PKB/Akt were unaffected (p > 0.05). Total SKAR protein, a downstream target of S6K1, and citrate synthase activity increased in Active rats (p < 0.05), though plasma insulin and glucose levels were unchanged (p > 0.05). Reduced mTOR/S6K1 signaling during chronic increases in physical activity may play an important regulatory role in the serine phosphorylation of IRS-1, which should be examined as a potential mechanism for attenuation of insulin resistance associated with increased IRS-1 serine phosphorylation.

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 · 10.1139/h07-149

Cites

49 of 49 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?

Endurance training inhibits mTOR/p70 S6K signaling and reduces IRS1 serine phosphorylation in rat skeletal muscle.
“Endurance training has been shown to inhibit mTOR/p70 S6K signaling and reduce IRS1 serine phosphorylation in rat skeletal muscle [157], and recent studies have demonstrated that AMPK is involved in the suppression of mTOR signaling [39].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [157]

Self-check

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

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

Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326 · see citing works
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,283 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
[1] Citrate synthase
Srere, P. A. (1969) · Methods in Enzymology · doi:10.1016/0076-6879(69)13005-0 · Cited by 2,005 · see citing works
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677 · see citing works
Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene
Araki, E., Lipes, M. A., Patti, M.-E., Brüning, J. C., Haag III, B., Johnson, R. S., & Kahn, C. R. (1994) · Nature · doi:10.1038/372186a0 · Cited by 1,252 · see citing works
Quantitation of Muscle Glycogen Synthesis in Normal Subjects and Subjects with Non-Insulin-Dependent Diabetes by<sup>13</sup>C Nuclear Magnetic Resonance Spectroscopy
Shulman, G. I., Rothman, D. L., Jue, T., Stein, P., DeFronzo, R. A., & Shulman, R. G. (1990) · New England Journal of Medicine · doi:10.1056/nejm199001253220403 · Cited by 1,248 · see citing works
Exercise, Glucose Transport, and Insulin Sensitivity
Goodyear, L. J., & Kahn, B. B. (1998) · Annual Review of Medicine · doi:10.1146/annurev.med.49.1.235 · Cited by 1,056 · see citing works
Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle
Winder, W. W., Holmes, B. F., Rubink, D. S., Jensen, E. B., Chen, M., & Holloszy, J. O. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.6.2219 · Cited by 709 · see citing works
Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1
Um, S. H., D'Alessio, D., & Thomas, G. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.05.003 · Cited by 690 · see citing works
Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle
Dreyer, H. C., Fujita, S., Cadenas, J. G., Chinkes, D. L., Volpi, E., & Rasmussen, B. B. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.113175 · Cited by 570 · see citing works
Self-citation
Increased Activation of the Mammalian Target of Rapamycin Pathway in Liver and Skeletal Muscle of Obese Rats: Possible Involvement in Obesity-Linked Insulin Resistance
Khamzina, L., Veilleux, A., Bergeron, S., & Marette, A. (2005) · Endocrinology · doi:10.1210/en.2004-0921 · Cited by 562 · see citing works
A Molecular Basis for Insulin Resistance
Paz, K., Hemi, R., LeRoith, D., Karasik, A., Elhanany, E., Kanety, H., & Zick, Y. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.47.29911 · Cited by 553 · see citing works
Amino Acid and Insulin Signaling via the mTOR/p70 S6 Kinase Pathway
Tremblay, F., & Marette, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106703200 · Cited by 536 · see citing works
Bidirectional modulation of insulin action by amino acids.
Patti, M., Brambilla, E., Luzi, L., Landaker, E. J., & Kahn, C. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1326 · Cited by 491 · see citing works
Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation
Tzatsos, A., & Kandror, K. V. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.63-76.2006 · Cited by 399 · see citing works
Exercise regulation of glucose transport in skeletal muscle.
Hayashi, T., Wojtaszewski, J., & Goodyear, L. (1997) · American Journal of Physiology · doi:10.1152/ajpendo.1997.273.6.e1039 · Cited by 394 · see citing works
Overactivation of S6 Kinase 1 as a Cause of Human Insulin Resistance During Increased Amino Acid Availability
Tremblay, F., Krebs, M., Dombrowski, L., Brehm, A., Bernroider, E., Roth, E., Nowotny, P., Waldhäusl, W., Marette, A., & Roden, M. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2674 · Cited by 370 · see citing works
Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2.
Bacquer, O. L., Petroulakis, E., Paglialunga, S., Poulin, F., Richard, D., Cianflone, K., & Sonenberg, N. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29528 · Cited by 365 · see citing works
Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle
Fujii, N., Hayashi, T., Hirshman, M. F., Smith, J. T., Habinowski, S. A., Kaijser, L., Mu, J., Ljungqvist, O., Birnbaum, M. J., Witters, L. A., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3073 · Cited by 351 · see citing works
Nutrient signalling in the regulation of human muscle protein synthesis
Fujita, S., Dreyer, H. C., Drummond, M. J., Glynn, E. L., Cadenas, J. G., Yoshizawa, F., Volpi, E., & Rasmussen, B. B. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.134593 · Cited by 339 · see citing works
Self-citation
Contraction signaling to glucose transport in skeletal muscle
Jessen, N., & Goodyear, L. J. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00175.2005 · Cited by 311 · see citing works
Reduced activation of phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes
Bouzakri, K., Roques, M., Gual, P., Espinosa, S., Guebre-Egziabher, F., Riou, J.-P., Laville, M., Le Marchand-Brustel, Y., Tanti, J.-F., & Vidal, H. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1319 · Cited by 305 · see citing works
Serine/Threonine Phosphorylation of IRS-1 Triggers Its Degradation
Pederson, T. M., Kramer, D. L., & Rondinone, C. M. (2001) · Diabetes · doi:10.2337/diabetes.50.1.24 · Cited by 300 · see citing works
Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase
Avruch, J., Hara, K., Lin, Y., Liu, M., Long, X., Ortiz-Vega, S., & Yonezawa, K. (2006) · Oncogene · doi:10.1038/sj.onc.1209882 · Cited by 297 · see citing works
Regulation of protein synthesis by insulin
Proud, C. G. (2006) · Biochemical Society Transactions · doi:10.1042/bst20060213 · Cited by 270 · see citing works
Invited review: Exercise training-induced changes in insulin signaling in skeletal muscle.
Zierath, J. (2002) · Journal of applied physiology · doi:10.1152/japplphysiol.00126.2002 · Cited by 229 · see citing works
The twentieth century struggle to decipher insulin signalling
Cohen, P. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2043 · Cited by 220 · see citing works
SKAR Is a Specific Target of S6 Kinase 1 in Cell Growth Control
Richardson, C. J., Brönstrup, M., Fingar, D. C., Jülich, K., Ballif, B. A., Gygi, S. P., & Blenis, J. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.061 · Cited by 198 · see citing works
Acute Reversal of the Enhanced Insulin Action in Trained Athletes: Association with Insulin Receptor Changes
Burstein, R., Polychronakos, C., Toews, C. J., MacDougall, J. D., Guyda, H. J., & Posner, B. I. (1985) · Diabetes · doi:10.2337/diab.34.8.756 · Cited by 171 · see citing works
Effect of exercise intensity on skeletal muscle malonyl-CoA and acetyl-CoA carboxylase
Rasmussen, B. B., & Winder, W. W. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.83.4.1104 · Cited by 158 · see citing works
Self-citation
Physically Active Subjects Should Be the Control Group
Booth, F. W., & Lees, S. J. (2006) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000205117.11882.65 · Cited by 124 · see citing works
Akt2 Is Essential for the Full Effect of Calorie Restriction on Insulin-Stimulated Glucose Uptake in Skeletal Muscle
McCurdy, C. E., & Cartee, G. D. (2005) · Diabetes · doi:10.2337/diabetes.54.5.1349 · Cited by 117 · see citing works
Time course changes in signaling pathways and protein synthesis in C2C12 myotubes following AMPK activation by AICAR.
Williamson, D. L., Bolster, D., Kimball, S., & Jefferson, L. (2006) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00566.2005 · Cited by 103 · see citing works
Endurance training increases skeletal muscle LKB1 and PGC-1α protein abundance: effects of time and intensity
Taylor, E. B., Lamb, J. D., Hurst, R. W., Chesser, D. G., Ellingson, W. J., Greenwood, L. J., Porter, B. B., Herway, S. T., & Winder, W. W. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00237.2005 · Cited by 102 · see citing works
Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats
Christ-Roberts, C. Y., Hunt, D. G., Hancock, J., García-Macedo, R., Mandarino, L. J., & Ivy, J. L. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00784.2001 · Cited by 92 · see citing works
Daily Exercise Reduces Fat, Protein and Body Mass in Male but not Female Rats
Cortright, R. N., Chandler, M. P., Lemon, P. W. R., & DiCarlo, S. E. (1997) · Physiology & Behavior · doi:10.1016/s0031-9384(97)00148-0 · Cited by 91 · see citing works
Self-citation
Recent advances in the regulation of the TOR pathway by insulin and nutrients
Avruch, J., Lin, Y., Long, X., Murthy, S., & Ortiz-Vega, S. (2004) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200501000-00010 · Cited by 91 · see citing works
Postcontraction insulin sensitivity: relationship with contraction protocol, glycogen concentration, and 5′ AMP-activated protein kinase phosphorylation
Kim, J., Solis, R. S., Arias, E. B., & Cartee, G. D. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00909.2003 · Cited by 60 · see citing works
Glucose uptake and GLUT-4 protein distribution in skeletal muscle of the obese Zucker rat
Brozinick, J. T., Etgen, G. J., Yaspelkis, B. B., & Ivy, J. L. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.1.r236 · Cited by 60 · see citing works
Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3β and p70S6K levels in rats
Zanchi, N. E., Filho, M. A. D. S., Lira, F. S., Neto, J. C. R., Yamashita, A. S., Carvalho, C. R. D. O., Seelaender, M. C. L., & Lancha, A. H. (2009) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1033-6 · Cited by 59 · see citing works
Exercise and insulin signaling: a historical perspective
Tomás, E., Zorzano, A., & Ruderman, N. B. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00267.2002 · Cited by 43 · see citing works
mTOR function in skeletal muscle: a focal point for overnutrition and exercise
Rivas, D. A., Lessard, S. J., & Coffey, V. G. (2009) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h09-073 · Cited by 40 · see citing works
Daily exercise-induced cardioprotection is associated with changes in calcium regulatory proteins in hypertensive rats
Collins, H. L., Loka, A. M., & DiCarlo, S. E. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00873.2004 · Cited by 40 · see citing works
Self-citation
Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes
Burstein, R., Polychronakos, C., Toews, C. J., et al. (1985) · Diabetes · doi:10.2337/diabetes.34.8.756 · Cited by 40 · see citing works
PRAS40: Target or modulator of mTORC1 signalling and insulin action?
Nascimento, E. B. M., & Ouwens, D. M. (2009) · Archives of Physiology and Biochemistry · doi:10.1080/13813450902988580 · Cited by 38 · see citing works
Harmonic content of electron-impact source functions in inductively coupled plasmas using an “on-the-fly” Monte Carlo technique
Sankaran, A., & Kushner, M. J. (2002) · Journal of Applied Physics · doi:10.1063/1.1487455 · Cited by 21 · see citing works
Chronic aerobic exercise enhances components of the classical and novel insulin signalling cascades in Sprague–Dawley rat skeletal muscle
Bernard, J. R., Crain, A., Rivas, D. A., Herr, H. J., Reeder, D. W., & Yaspelkis, B. B. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2005.01408.x · Cited by 13 · see citing works
AMINO ACIDS AND INSULIN
Jackson, W. P. U. (1972) · Transactions of the Royal Society of South Africa · doi:10.1080/00359197209519409 · Cited by 2 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

Srere PA. Citrate synthase. Methods Enzymol. 1969;13:3–6. [Google Scholar]

Sorted by citations

AMPK and Exercise: Glucose Uptake and Insulin Sensitivity
O'Neill, H. M. (2013) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2013.37.1.1 · Cited by 295 · see citing works
The Cardioprotection of the Insulin-Mediated PI3K/Akt/mTOR Signaling Pathway
Yao, H., Han, X.-Y., & Han, X. (2014) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-014-0089-9 · Cited by 179 · see citing works
Daily exercise vs. caloric restriction for prevention of nonalcoholic fatty liver disease in the OLETF rat model
Rector, R. S., Uptergrove, G. M., Morris, E. M., Borengasser, S. J., Laughlin, M. H., Booth, F. W., Thyfault, J. P., & Ibdah, J. A. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00510.2010 · Cited by 152 · see citing works
Clinical problems caused by obesity
Kyrou, I., Randeva, H. S., Barber, T., Tsigos, C., Kaltsas, G. A., & Weickert, M. O. (2022) · Warwick Research Archive Portal (University of Warwick) · doi:10.82444/warw.33841351 · Cited by 127 · see citing works
and Alzheimer's disease
Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R., & Cowart, M. (2010) · Cited by 125 · see citing works
TOR-centric view on insulin resistance and diabetic complications: perspective for endocrinologists and gerontologists
Blagosklonny, M. V. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.506 · Cited by 116 · see citing works
Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence
Yaribeygi, H., Maleki, M., Sathyapalan, T., Jamialahmadi, T., & Sahebkar, A. (2021) · Journal of Diabetes Research · doi:10.1155/2021/7796727 · Cited by 91 · see citing works
Hormesis does not make sense except in the light of TOR-driven aging
Blagosklonny, M. V. (2011) · Aging · doi:10.18632/aging.100411 · Cited by 79 · see citing works
Rapamycin reverses insulin resistance (IR) in high-glucose medium without causing IR in normoglycemic medium
Leontieva, O. V., Demidenko, Z. N., & Blagosklonny, M. V. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.178 · Cited by 68 · see citing works
Improvement of obesity-linked skeletal muscle insulin resistance by strength and endurance training
Meo, S. D., Iossa, S., & Venditti, P. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0186 · Cited by 62 · see citing works
Rapamycin-Induced Glucose Intolerance: Hunger or Starvation Diabetes
Blagosklonny, M. V. (2011) · Cell Cycle · doi:10.4161/cc.10.24.18595 · Cited by 59 · see citing works
Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3β and p70S6K levels in rats
Zanchi, N. E., Filho, M. A. D. S., Lira, F. S., Neto, J. C. R., Yamashita, A. S., Carvalho, C. R. D. O., Seelaender, M. C. L., & Lancha, A. H. (2009) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1033-6 · Cited by 59 · see citing works
Lipid-induced mTOR activation in rat skeletal muscle reversed by exercise and 5′-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside
Rivas, D. A., Yaspelkis, B. B., Hawley, J. A., & Lessard, S. J. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0202 · Cited by 59 · see citing works
Downhill Running Excessive Training Inhibits Hypertrophy in Mice Skeletal Muscles with Different Fiber Type Composition
da Rocha, A. L., Pereira, B. C., Pauli, J. R., de Souza, C. T., Teixeira, G. R., Lira, F. S., Cintra, D. E., Ropelle, E. R., Júnior, C. R. B., & da Silva, A. S. R. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25197 · Cited by 57 · see citing works
mTOR and tau phosphorylated proteins in the hippocampal tissue of rats with type 2 diabetes and Alzheimer’s disease
Ma, Y., Wu, D., & LIU, J.-K. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.1186 · Cited by 48 · see citing works
Koschei the immortal and anti-aging drugs
Blagosklonny, M. V. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.520 · Cited by 41 · see citing works
mTOR function in skeletal muscle: a focal point for overnutrition and exercise
Rivas, D. A., Lessard, S. J., & Coffey, V. G. (2009) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h09-073 · Cited by 40 · see citing works
Contractile activity-induced mitochondrial biogenesis and mTORC1
Carter, H. N., & Hood, D. A. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00156.2012 · Cited by 40 · see citing works
Enhanced skeletal muscle insulin sensitivity after acute resistance-type exercise is upregulated by rapamycin-sensitive mTOR complex 1 inhibition
Kido, K., Sase, K., Yokokawa, T., & Fujita, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-65397-z · Cited by 40 · see citing works
PRAS40: Target or modulator of mTORC1 signalling and insulin action?
Nascimento, E. B. M., & Ouwens, D. M. (2009) · Archives of Physiology and Biochemistry · doi:10.1080/13813450902988580 · Cited by 38 · see citing works
Divergent physiological characteristics and responses to endurance training among inbred mouse strains
Kilikevičius, A., Venckūnas, T., Zelniene, R., Carroll, A. M., Lionikaite, S., Ratkevičius, A., & Lionikas, A. (2012) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.2012.01451.x · Cited by 34 · see citing works
Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet
Stanišić, J., Korićanac, G., Ćulafić, T., Romić, S., Stojiljković, M., Kostić, M., Pantelić, M., & Tepavčević, S. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.11.032 · Cited by 34 · see citing works
Modulating mTOR Signaling as a Promising Therapeutic Strategy for Atherosclerosis
Poznyak, A. V., Sukhorukov, V. N., Zhuravlev, A. D., Orekhov, N. A., Kalmykov, V. A., & Orekhov, A. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031153 · Cited by 30 · see citing works
Genome-wide DNA methylation profiles provide insight into epigenetic regulation of red and white muscle development in Chinese perch Siniperca chuatsi
Pan, Y., Chen, L., Cheng, J. R., Zhu, X., Wu, P., Bao, L., Chu, W., He, S., Liang, X., & Zhang, J. (2021) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2021.110647 · Cited by 23 · see citing works
Detraining-induced alterations in metabolic and fitness markers after a multicomponent exercise-training program in older men
Ratel, S., Gryson, C., Rance, M., Penando, S., Bonhomme, C., Ruyet, P. L., Duclos, M., Boirie‌, Y., & Walrand, S. (2012) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h11-130 · Cited by 25 · see citing works
Myofibrillar protein synthesis rates are increased in chronically exercised skeletal muscle despite decreased anabolic signaling
Langer, H. T., West, D. W. D., Senden, J. M., Spuler, S., van Loon, L. J. C., & Baar, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-11621-x · Cited by 21 · see citing works
Reduced Ribosomal Protein S6 Phosphorylation following Progressive Resistance Exercise in Growing Adolescent Rats
Hellyer, N., Nokleby, J. J., Thicke, B. M., Zhan, W., Sieck, G., & Mantilla, C. (2012) · Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e318231abc9 · Cited by 21 · see citing works
Mammalian target of rapamycin pathway is up-regulated by both acute endurance exercise and chronic muscle contraction in rat skeletal muscle
Edgett, B. A., Fortner, M. L., Bonen, A., & Gurd, B. J. (2013) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2012-0405 · Cited by 20 · see citing works
Phycocyanin attenuates skeletal muscle damage and fatigue via modulation of Nrf2 and IRS-1/AKT/mTOR pathway in exercise-induced oxidative stress in rats
Puengpan, S., Phetrungnapha, A., Sattayakawee, S., & Tunsophon, S. (2024) · PLoS ONE · doi:10.1371/journal.pone.0310138 · Cited by 16 · see citing works
Effects of Acute Muscle Contraction on the Key Molecules in Insulin and Akt Signaling in Skeletal Muscle in Health and in Insulin Resistant States
Mann, G., Riddell, M. C., & Adegoke, O. A. J. (2022) · Diabetology · doi:10.3390/diabetology3030032 · Cited by 14 · see citing works
Voluntary physical activity prevents insulin resistance in a tissue specific manner
Sarvas, J. L., Otis, J. S., Khaper, N., & Lees, S. J. (2015) · Physiological Reports · doi:10.14814/phy2.12277 · Cited by 13 · see citing works
Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice
Xu, M., Liu, X., Bao, P., Wang, Y., Zhu, X., Liu, Y., Ni, X., & Lu, J. (2022) · Antioxidants · doi:10.3390/antiox11112216 · Cited by 12 · see citing works
Investigation of PI3K/PKB/mTOR/S6K1 signaling pathway in relationship of type 2 diabetes and Alzheimer's disease.
Ma, Y., Wu, D., Zhang, W., Liu, J., Chen, S., & Hua, B. (2015) · PubMed Central · Cited by 11 · see citing works
Comparative genome-wide methylation analysis reveals epigenetic regulation of muscle development in grass carp (Ctenopharyngodon idellus) fed with whole faba bean
Li, Y., Fu, B., Zhang, J., Wang, G., Tian, J., Li, H., Xia, Y. L., Xie, J., & Yu, E. (2022) · PeerJ · doi:10.7717/peerj.14403 · Cited by 8 · see citing works
TorS ‐ Reframing a rational for type 2 diabetes treatment
Bar‐Tana, J. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3712 · Cited by 2 · see citing works
Alterations in Cardiac Electrophysiology After Spinal Cord Injury and Implications for Exercise
Lujan, H. L., & DiCarlo, S. E. (2016) · Springer eBooks · doi:10.1007/978-1-4939-6664-6_5 · Cited by 1 · see citing works
Self-citation
The role of the perilipin proteins in regulating intramuscular lipid metabolism: effect of exercise training
Shepherd, S. O. (2013) · University of Birmingham Institutional Research Archive (University of Birmingham)
The Impact of Reduced-Exertion High-Intensity Interval Training on Insulin Sensitivity and Aerobic Capacity
Metcalfe, R. S. (2015) · The University of Bath Online Publications Store (The University of Bath) · doi:10.13140/rg.2.1.4944.0088
Sex differences in the cardiac beta-adrenergic receptor contractile response
McIntosh, V. J. (2012) · Human Biology
Apport de l’exercice physique en pratique cancérologique
Bouillet, T., Chouahnia, K., & Serin, D. (2010) · Springer eBooks · doi:10.1007/978-2-287-79501-5_11
mTOR Pathway is Up-regulated by Both Acute Endurance Exercise and Chronic Muscle Contraction in Rat Skeletal Muscle
Edgett, B. A. (2012) · QSpace (Queen's University Library)
Spinal Cord Injury: An Under Recognized Cardiovascular Disease Risk Factor
DiCarlo, S. E. (2018) · Journal of Cardiology & Cardiovascular Therapy · doi:10.19080/jocct.2018.09.555756
Self-citation
The Stress and Strain of Triathlon Racing in Different Thermal Environments
Creasy, R. H. (2019) · Otago University Research Archive (University of Otago) · Cited by 1 · see citing works
Skeletal muscle metabolic flexibility: contribution of genetics and lifestyle
Rivas, D. A. (2011) · RMIT Research Repository (RMIT University Library) · doi:10.25439/rmt.27340623
Effects of long-term voluntary running exercise and caloric restriction during development on intracellular signaling in female rat skeletal muscles
Ogawa, S., Hasegawa, T., & Yoshihara, T. (2025) · 体力科學 · doi:10.7600/jspfsm.74.155

A Chronic Increase in Energy Expenditure Inhibits S6K1 and Reduces IRS-1 Serine Phosphorylation in Muscle
Glynn, E. L., Lujan, H. L., Kramer, V. J., Drummond, M. J., DiCarlo, S. E., & Rasmussen, B. B. (2007) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000272899.83864.8e
Self-citation
Phosphorylation of muscle Akt, AS160, and S6K1 are reduced following 8 weeks of increased physical activity in fasting rats
Fry, C. S., Glynn, E. L., Lujan, H. L., DiCarlo, S. E., & Rasmussen, B. B. (2008) · The FASEB Journal · doi:10.1096/fasebj.22.1_supplement.959.18
Self-citation
Modulation of Insulin Signaling via Resistance Exercise
Hamilton, D. L., MacKenzie, M. G., & Baar, K. (2008) · The FASEB Journal · doi:10.1096/fasebj.22.1_supplement.959.21
[The relationship between mTor/S6K1 signaling pathway and insulin resistance and the study of aerobic exercise on this pathway].
Niu, Y., Yuan, H., Zhang, N., & Fu, L. (2010) · PubMed · Cited by 2 · see citing works
Insulin resistance and muscle insulin receptor substrate-1 serine hyperphosphorylation
Stuart, C. A., Howell, M. E. A., Cartwright, B. M., McCurry, M. P., Lee, M. L., Ramsey, M. W., & Stone, M. H. (2014) · Physiological Reports · doi:10.14814/phy2.12236 · Cited by 22 · see citing works

Authors: Glynn, E. L., Lujan, H. L., Kramer, V. J., Drummond, M. J., DiCarlo, S. E., & Rasmussen, B. B.
Affiliations: Wayne State University (US)
ORCID: Glynn, Erin L.
Lujan, Heidi L.
Drummond, Micah J.
DiCarlo, Stephen E.
Rasmussen, Blake B.
Venue: Applied Physiology, Nutrition, and Metabolism
Publisher: Canadian Science Publishing
Published: 2008-02
Volume: 33
Issue: 1
Pages: 93-101
ISSN: 1715-5312 (ISSN-L)
1715-5320
DOI: 10.1139/h07-149
PMC: PMC2706125
OpenAlex: W2147722362
Cited by: 45
References: 49
Citations by year: 2025: 1 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 3 · 2013: 4 · 2012: 7
FWCI: 1.23
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.nrcresearchpress.com/page/about/CorporateTextAndDataMining (tdm)
Locations: Applied Physiology, Nutrition, and Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (P30AG024832)
National Heart, Lung, and Blood Institute (R01HL074122)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR049877)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007539)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: physical activity, endurance training, mTOR signaling, S6K1, IRS-1 serine phosphorylation, insulin resistance, skeletal muscle, soleus muscle, insulin sensitivity, citrate synthase, Akt, AMPKα, 4E-BP1, elongation factor 2
MeSH terms: Animals, Blood Glucose, Citrate (si)-Synthase, Insulin, Insulin Resistance, Male, Phosphorylation, Physical Conditioning, Animal, Protein Kinases, Serine, Blotting, Western, Rats, Sprague-Dawley, Muscle, Skeletal, Lactic Acid, Ribosomal Protein S6 Kinases, Adaptor Proteins, Signal Transducing, STAT1 Transcription Factor, Rats, Insulin Receptor Substrate Proteins, TOR Serine-Threonine Kinases

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

A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks