In vivo exercise followed by in vitro contraction additively elevates subsequent insulin-stimulated glucose transport by rat skeletal muscle
Open accessAbstract
The cellular mechanisms whereby prior exercise enhances insulin-stimulated glucose transport (GT) are not well understood. Previous studies suggested that a prolonged increase in phosphorylation of Akt substrate of 160 kDa (AS160) may be important for the postexercise increase in insulin sensitivity. In the current study, the effects of in vivo exercise and in vitro contraction on subsequent insulin-stimulated GT were studied separately and together. Consistent with results from previous studies, prior exercise resulted in an increase in AS160 642 Thr phosphorylation immediately after exercise in rat epitrochlearis muscles, and this increase remained 3 h postexercise concomitant with enhanced insulin-stimulated GT. For experiments with in vitro contraction, isolated rat epitrochlearis muscles were electrically stimulated to contract in the presence or absence of rat serum. As expected, insulin-stimulated GT measured 3 h after electrical stimulation in serum, but not after electrical stimulation without serum, exceeded resting controls. Immediately after electrical stimulation with or without serum, phosphorylation of both AS160 (detected by phospho-Akt substrate, PAS, antibody, or phospho-642 Thr antibody) and its paralog TBC1D1 (detected by phospho-237 Ser antibody) was increased. However, both AS160 and TBC1D1 phosphorylation had reversed to resting values at 3 h poststimulation with or without serum. Increasing the amount of exercise (from 1 to 2 h) or electrical stimulation (from 5 to 10 tetani) did not further elevate insulin-stimulated GT. In contrast, the combination of prior exercise and electrical stimulation had an additive effect on the subsequent increase in insulin-stimulated GT, suggesting that these exercise and electrical stimulation protocols may amplify insulin-stimulated GT through distinct mechanisms, with a persistent increase in AS160 phosphorylation potentially important for increased insulin sensitivity after exercise, but not after in vitro contraction.
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TBC1D4 T642 and PAS phosphorylation is increased immediately after exercise and 3 hours postexercise, consistent with enhanced insulin-stimulated glucose uptake; following in vitro contractions TBC1D4 phosphorylation returned to resting levels 3 hours postexercise despite having an additive effect on glucose uptake in response to insulin.
“These studies have found that whilst TBC1D4 T642 and PAS phosphorylation is increased immediately after exercise and 3 hours postexercise consistent with enhanced insulin-stimulated glucose uptake; following in vitro contractions TBC1D4 phosphorylation had returned to resting levels 3 hours postexercise despite having an additive effect on glucose uptake in response to insulin [123].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [123]
Cites
Insulin-stimulated Phosphorylation of a Rab GTPase-activating Protein Regulates GLUT4 Translocation
Sano, H., Kane, S., Sano, E., Mı̂inea, C. P., Asara, J. M., Lane, W. S., Garner, C. W., & Lienhard, G. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300063200 · Cited by 964 · see citing works
A comparison of three methods of glycogen measurement in tissues
Passonneau, J. V., & Lauderdale, V. R. (1974) · Analytical Biochemistry · doi:10.1016/0003-2697(74)90248-6 · Cited by 744 · see citing works
A Method to Identify Serine Kinase Substrates
Kane, S., Sano, H., Liu, S. C. H., Asara, J. M., Lane, W. S., Garner, C. C., & Lienhard, G. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200198200 · Cited by 529 · see citing works
Muscle Glucose Metabolism following Exercise in the Rat
Richter, E. A., Garetto, L. P., Goodman, M. N., & Ruderman, N. B. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110517 · Cited by 510 · see citing works
Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic
Sakamoto, K., & Holman, G. D. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90331.2008 · Cited by 481 · see citing works
Mîinea, C. P., Sano, H., Kane, S., Sano, E., Fukuda, M., Peränen, J., Lane, W. S., & Lienhard, G. E. (2005) · Biochemical Journal · doi:10.1042/bj20050887 · Cited by 449 · see citing works
Insulin signaling and insulin sensitivity after exercise in human skeletal muscle
Wojtaszewski, J. F., Hansen, B. F., Gade, Kiens, B., Markuns, J. F., Goodyear, L. J., & Richter, E. A. (2000) · Diabetes · doi:10.2337/diabetes.49.3.325 · Cited by 382 · see citing works
Skeletal Muscle Glucose Uptake During Exercise: How is it Regulated?
Rose, A. J., & Richter, E. A. (2005) · Physiology · doi:10.1152/physiol.00012.2005 · Cited by 371 · see citing works
Prolonged increase in insulin-stimulated glucose transport in muscle after exercise
Cartee, G. D., Young, D. A., Sleeper, M. D., Zierath, J., Wallberg-Henriksson, H., & Holloszy, J. O. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.256.4.e494 · Cited by 342 · see citing works
Self-citationActivation of p38 MAP kinase enhances sensitivity of muscle glucose transport to insulin
Geiger, P. C., Wright, D. C., Han, D., & Holloszy, J. O. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00477.2004 · Cited by 306 · see citing works
Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects with Type 2 Diabetes
Sriwijitkamol, A., Coletta, D. K., Wajcberg, E., Balbontin, G. B., Reyna, S. M., Barrientes, J., Eagan, P. A., Jenkinson, C. P., Cersosimo, E., DeFronzo, R. A., et al. (2007) · Diabetes · doi:10.2337/db06-1119 · Cited by 304 · see citing works
Bruss, M. D., Arias, E. B., Lienhard, G. E., & Cartee, G. D. (2005) · Diabetes · doi:10.2337/diabetes.54.1.41 · Cited by 273 · see citing works
Self-citationTaylor, E. B., An, D., Kramer, H. F., Yu, H., FUJII, N. L., Röckl, K. S. C., Bowles, N. P., Hirshman, M. F., Xie, J., Feener, E. P., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708839200 · Cited by 268 · see citing works
Contractile C2C12myotube model for studying exercise-inducible responses in skeletal muscle
Nedachi, T., Fujita, H., & Kanzaki, M. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90280.2008 · Cited by 247 · see citing works
Self-citationActivation of AMP kinase enhances sensitivity of muscle glucose transport to insulin
Fisher, J. S., Gao, J., Han, D.-H., Holloszy, J. O., & Nolte, L. A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2002.282.1.e18 · Cited by 244 · see citing works
Wojtaszewski, J. F. P., Higaki, Y., Hirshman, M. F., Michael, M. D., Dufresne, S. D., Kahn, C. R., & Goodyear, L. J. (1999) · Journal of Clinical Investigation · doi:10.1172/jci7961 · Cited by 234 · see citing works
Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators
Chen, S., Murphy, J. E., Toth, R. L., Campbell, D. G., MORRICE, N. A., & MacKintosh, C. (2007) · Biochemical Journal · doi:10.1042/bj20071114 · Cited by 207 · see citing works
Substrate specificity and effect on GLUT4 translocation of the Rab GTPase-activating protein Tbc1d1
Roach, W. G., Chavez, J. A., Mı̂inea, C. P., & Lienhard, G. E. (2007) · Biochemical Journal · doi:10.1042/bj20061798 · Cited by 192 · see citing works
Hansen, P. A., Nolte, L. A., Chen, M. M., & Holloszy, J. O. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.85.4.1218 · Cited by 189 · see citing works
Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport
Cartee, G. D., & Wojtaszewski, J. F. P. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-026 · Cited by 183 · see citing works
Self-citationPehmøller, C., Treebak, J. T., Birk, J. B., Chen, S., MacKintosh, C., Hardie, D. G., Richter, E. A., & Wojtaszewski, J. F. P. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00115.2009 · Cited by 171 · see citing works
Gulve, E. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.5.1679 · Cited by 165 · see citing works
A forty-year memoir of research on the regulation of glucose transport into muscle
Holloszy, J. O. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00463.2002 · Cited by 135 · see citing works
Funai, K., Schweitzer, G. G., Sharma, N., Kanzaki, M., & Cartee, G. D. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00194.2009 · Cited by 119 · see citing works
Self-citationPotential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle
Treebak, J. T., Frøsig, C., Pehmøller, C., Chen, S., Maarbjerg, S. J., Brandt, N., MacKintosh, C., Zierath, J. R., Hardie, D. G., Kiens, B., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1294-y · Cited by 119 · see citing works
Prior exercise increases phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle
Arias, E. B., Kim, J., Funai, K., & Cartee, G. D. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00602.2006 · Cited by 118 · see citing works
Self-citationExercise increases susceptibility of muscle glucose transport to activation by various stimuli
Cartee, G. D., & Holloszy, J. O. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.258.2.e390 · Cited by 113 · see citing works
Self-citationEffect of exercise on insulin receptor binding and kinase activity in skeletal muscle
Treadway, J. L., James, D. E., Burcel, E., & Ruderman, N. B. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.256.1.e138 · Cited by 86 · see citing works
Growth hormone reduces glucose transport but not GLUT-1 or GLUT-4 in adult and old rats
Cartee, G. D., & Bohn, E. E. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.5.e902 · Cited by 85 · see citing works
Self-citationHamada, T., Arias, E. B., & Cartee, G. D. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00416.2006 · Cited by 84 · see citing works
Self-citationExercise and Insulin: Convergence or Divergence at AS160 and TBC1D1?
Cartee, G. D., & Funai, K. (2009) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e3181b7b7c5 · Cited by 77 · see citing works
Self-citationFunai, K., & Cartee, G. D. (2009) · Diabetes · doi:10.2337/db08-1477 · Cited by 76 · see citing works
Self-citationInsulin Signaling After Exercise in Insulin Receptor Substrate-2-Deficient Mice
Howlett, K. F., Sakamoto, K., Hirshman, M. F., Aschenbach, W. G., Dow, M. A., White, M. F., & Goodyear, L. J. (2002) · Diabetes · doi:10.2337/diabetes.51.2.479 · Cited by 74 · see citing works
Reversal of enhanced muscle glucose transport after exercise: roles of insulin and glucose
Gulve, E. A., Cartee, G. D., Zierath, J. R., Corpus, V. M., & Holloszy, J. O. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.259.5.e685 · Cited by 73 · see citing works
Self-citationContraction-induced increase in muscle insulin sensitivity: requirement for a serum factor
Gao, J., Gulve, E. A., & Holloszy, J. O. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.2.e186 · Cited by 62 · see citing works
Persistent effects of exercise on skeletal muscle glucose transport across the life-span of rats
Cartee, G. D., Briggs-Tung, C., & Kietzke, E. W. (1993) · Journal of Applied Physiology · doi:10.1152/jappl.1993.75.2.972 · Cited by 47 · see citing works
Self-citationNolte, L. A., Gulve, E. A., & Holloszy, J. O. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.76.5.2054 · Cited by 38 · see citing works
Effects of exercise on insulin binding to human muscle
Bonen, A., Tan, M. H., Clune, P., & Kirby, R. (1985) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1985.248.4.e403 · Cited by 31 · see citing works
Blair, D. R., Funai, K., Schweitzer, G. G., & Cartee, G. D. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.91003.2008 · Cited by 31 · see citing works
Self-citationDumke, C. L., Kim, J., Arias, E. B., & Cartee, G. D. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00854.2001 · Cited by 25 · see citing works
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O'Neill, H. M. (2013) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2013.37.1.1 · Cited by 295 · see citing works
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Kjøbsted, R., Munk-Hansen, N., Birk, J. B., Foretz, M., Viollet, B., Björnholm, M., Zierath, J. R., Treebak, J. T., & Wojtaszewski, J. F. P. (2017) · Diabetes · doi:10.2337/db16-0530 · Cited by 178 · see citing works
Sjøberg, K. A., Frøsig, C., Kjøbsted, R., Sylow, L., Kleinert, M., Betik, A. C., Shaw, C. S., Kiens, B., Wojtaszewski, J. F. P., Rattigan, S., et al. (2017) · Diabetes · doi:10.2337/db16-1327 · Cited by 164 · see citing works
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Maarbjerg, S. J., Sylow, L., & Richter, E. A. (2011) · Acta Physiologica · doi:10.1111/j.1748-1716.2011.02267.x · Cited by 104 · see citing works
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Kjøbsted, R., Roll, J. L. W., Jørgensen, N. O., Birk, J. B., Foretz, M., Viollet, B., Chadt, A., Al-Hasani, H., & Wojtaszewski, J. F. P. (2019) · Diabetes · doi:10.2337/db19-0050 · Cited by 97 · see citing works
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- Authors
- Funai, K., Schweitzer, G. G., Castorena, C. M., Kanzaki, M., & Cartee, G. D.
- Affiliations
- Muscle Biology Laboratory, School of Kinesiology and
- Tohoku University (JP)
- University of Michigan (US)
- Corresponding author
- Cartee, Gregory D.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2010-05
- Volume
- 298
- Issue
- 5
- Pages
- E999-E1010
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2867374
- OpenAlex
- W2153123820
- Cited by
- 63
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 10 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 2 · 2014: 9 · 2013: 3 · 2012: 5
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG010026)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK020572, DK071771, R01DK071771)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- insulin-stimulated glucose transport, physical activity, electrical stimulation, AS160 phosphorylation, insulin sensitivity, skeletal muscle, epitrochlearis muscle, Akt substrates, additive effects
- MeSH terms
- Analysis of Variance, Animals, Biological Transport, Electric Stimulation, Physical Exertion, Glucose, Glycogen, Insulin, Male, Muscle Contraction, Phosphorylation, Time Factors, Blotting, Western, Rats, Wistar, Muscle, Skeletal, GTPase-Activating Proteins, Immunoprecipitation, Glucose Transporter Type 4, Rats
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