Insulin responsiveness in metabolic syndrome after eight weeks of cycle training
Charles A Stuart, Mark A South, Michelle L Lee, Melanie P McCurry, Mary E A Howell, Michael W Ramsey, Michael H Stone, Charles A Stuart, Mark A South, Michelle L Lee, Melanie P McCurry, Mary E A Howell, Michael W Ramsey, Michael H Stone
Abstract
Introduction: Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome.
Methods: Eighteen nondiabetic, sedentary subjects, 11 with the metabolic syndrome, participated in 8 wk of increasing intensity stationary cycle training.
Results: Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (V·O 2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. The activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of type 2× fibers decreased with a concomitant increase in type 2a mixed fibers in the control subjects, but in metabolic syndrome, type 2× fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups, and GLUT4 expression increased in the metabolic syndrome subjects. The excess phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1.
Conclusions: In the absence of weight loss, the cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis and increased the expression of insulin receptors and GLUT4 in muscle but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337, and this is not ameliorated by 8 wk of endurance exercise training.
Conflict of interest statement
Disclosures. The authors have no conflicts of interest to disclose. The results of the present study do not constitute endorsement by the American College of Sports Medicine.
Figures
![Figure 1. Insulin responsiveness quantified by euglycemic…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3800492/bin/nihms490538f1.jpg)
![Figure 2. Change in muscle fiber composition…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3800492/bin/nihms490538f2.jpg)
Figure 3. The impact of exercise training…
Figure 3. The impact of exercise training on muscle expression of the insulin receptor, IRS-1,…
Figure 4. Fiber-specific changes in expression of…
Figure 4. Fiber-specific changes in expression of activated AMPK and mitochondrial marker ATP synthase
Since…
Figure 5. Cycle training impact on tyrosine…
Figure 5. Cycle training impact on tyrosine and serine phosphorylation of muscle IRS-1
Panels A,…
- Muscle hypertrophy in prediabetic men after 16 wk of resistance training.Stuart CA, Lee ML, South MA, Howell MEA, Stone MH. Stuart CA, et al. J Appl Physiol (1985). 2017 Oct 1;123(4):894-901. doi: 10.1152/japplphysiol.00023.2017. Epub 2017 Jun 29. J Appl Physiol (1985). 2017. PMID: 28663372 Free PMC article.
- Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness.Stuart CA, McCurry MP, Marino A, South MA, Howell ME, Layne AS, Ramsey MW, Stone MH. Stuart CA, et al. J Clin Endocrinol Metab. 2013 May;98(5):2027-36. doi: 10.1210/jc.2012-3876. Epub 2013 Mar 20. J Clin Endocrinol Metab. 2013. PMID: 23515448 Free PMC article.
- Cycle training increased GLUT4 and activation of mammalian target of rapamycin in fast twitch muscle fibers.Stuart CA, Howell ME, Baker JD, Dykes RJ, Duffourc MM, Ramsey MW, Stone MH. Stuart CA, et al. Med Sci Sports Exerc. 2010 Jan;42(1):96-106. doi: 10.1249/MSS.0b013e3181ad7f36. Med Sci Sports Exerc. 2010. PMID: 20010125 Free PMC article.
- Human Skeletal Muscle Mitochondrial Adaptations Following Resistance Exercise Training.Parry HA, Roberts MD, Kavazis AN. Parry HA, et al. Int J Sports Med. 2020 Jun;41(6):349-359. doi: 10.1055/a-1121-7851. Epub 2020 Mar 11. Int J Sports Med. 2020. PMID: 32162291 Review.
- Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training.Roberts CK, Hevener AL, Barnard RJ. Roberts CK, et al. Compr Physiol. 2013 Jan;3(1):1-58. doi: 10.1002/cphy.c110062. Compr Physiol. 2013. PMID: 23720280 Free PMC article. Review.
- Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle.Bengtsen M, Winje IM, Eftestøl E, Landskron J, Sun C, Nygård K, Domanska D, Millay DP, Meza-Zepeda LA, Gundersen K. Bengtsen M, et al. PLoS Genet. 2021 Nov 9;17(11):e1009907. doi: 10.1371/journal.pgen.1009907. eCollection 2021 Nov. PLoS Genet. 2021. PMID: 34752468 Free PMC article.
- Skeletal Muscle Proteomic Profile Revealed Gender-Related Metabolic Responses in a Diet-Induced Obesity Animal Model.Moriggi M, Belloli S, Barbacini P, Murtaj V, Torretta E, Chaabane L, Canu T, Penati S, Malosio ML, Esposito A, Gelfi C, Moresco RM, Capitanio D. Moriggi M, et al. Int J Mol Sci. 2021 Apr 28;22(9):4680. doi: 10.3390/ijms22094680. Int J Mol Sci. 2021. PMID: 33925229 Free PMC article.
- Weight loss is linearly associated with a reduction of the insulin response to an oral glucose test in Icelandic horses.Delarocque J, Frers F, Huber K, Feige K, Warnken T. Delarocque J, et al. BMC Vet Res. 2020 May 24;16(1):151. doi: 10.1186/s12917-020-02356-w. BMC Vet Res. 2020. PMID: 32448298 Free PMC article.
- Update on the effects of physical activity on insulin sensitivity in humans.Bird SR, Hawley JA. Bird SR, et al. BMJ Open Sport Exerc Med. 2017 Mar 1;2(1):e000143. doi: 10.1136/bmjsem-2016-000143. eCollection 2016. BMJ Open Sport Exerc Med. 2017. PMID: 28879026 Free PMC article. Review.
- Muscle hypertrophy in prediabetic men after 16 wk of resistance training.Stuart CA, Lee ML, South MA, Howell MEA, Stone MH. Stuart CA, et al. J Appl Physiol (1985). 2017 Oct 1;123(4):894-901. doi: 10.1152/japplphysiol.00023.2017. Epub 2017 Jun 29. J Appl Physiol (1985). 2017. PMID: 28663372 Free PMC article.
- Controlled Clinical Trial
- Research Support, N.I.H., Extramural
- Adult
- Bicycling / physiology
- Body Composition
- Body Weight
- Case-Control Studies
- Exercise Therapy*
- Female
- Glucose Transporter Type 4 / metabolism
- Humans
- Insulin
- Insulin Receptor Substrate Proteins / metabolism
- Insulin Resistance*
- Male
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / therapy*
- Middle Aged
- Mitochondrial Proton-Translocating ATPases / metabolism
- Muscle Fibers, Fast-Twitch / cytology
- Muscle Fibers, Fast-Twitch / metabolism
- Muscle Fibers, Slow-Twitch / cytology
- Muscle Fibers, Slow-Twitch / metabolism
- Muscle Strength
- Muscle, Skeletal / cytology*
- Muscle, Skeletal / enzymology
- Muscle, Skeletal / metabolism*
- Oxygen Consumption
- Phosphorylation
- Phosphotransferases (Phosphate Group Acceptor) / metabolism
- Receptor, Insulin / metabolism
- TOR Serine-Threonine Kinases / metabolism
- Young Adult
- Glucose Transporter Type 4
- Insulin
- Insulin Receptor Substrate Proteins
- SLC2A4 protein, human
- MTOR protein, human
- Receptor, Insulin
- TOR Serine-Threonine Kinases
- AMP-dependent kinase (ATP-forming)
- Phosphotransferases (Phosphate Group Acceptor)
- Mitochondrial Proton-Translocating ATPases
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3. The impact of exercise training…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3800492/bin/nihms490538f3.jpg)
Figure 4. Fiber-specific changes in expression of…
Figure 4. Fiber-specific changes in expression of activated AMPK and mitochondrial marker ATP synthase
Since…
Figure 5. Cycle training impact on tyrosine…
Figure 5. Cycle training impact on tyrosine and serine phosphorylation of muscle IRS-1
Panels A,…
- Muscle hypertrophy in prediabetic men after 16 wk of resistance training.Stuart CA, Lee ML, South MA, Howell MEA, Stone MH. Stuart CA, et al. J Appl Physiol (1985). 2017 Oct 1;123(4):894-901. doi: 10.1152/japplphysiol.00023.2017. Epub 2017 Jun 29. J Appl Physiol (1985). 2017. PMID: 28663372 Free PMC article.
- Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness.Stuart CA, McCurry MP, Marino A, South MA, Howell ME, Layne AS, Ramsey MW, Stone MH. Stuart CA, et al. J Clin Endocrinol Metab. 2013 May;98(5):2027-36. doi: 10.1210/jc.2012-3876. Epub 2013 Mar 20. J Clin Endocrinol Metab. 2013. PMID: 23515448 Free PMC article.
- Cycle training increased GLUT4 and activation of mammalian target of rapamycin in fast twitch muscle fibers.Stuart CA, Howell ME, Baker JD, Dykes RJ, Duffourc MM, Ramsey MW, Stone MH. Stuart CA, et al. Med Sci Sports Exerc. 2010 Jan;42(1):96-106. doi: 10.1249/MSS.0b013e3181ad7f36. Med Sci Sports Exerc. 2010. PMID: 20010125 Free PMC article.
- Human Skeletal Muscle Mitochondrial Adaptations Following Resistance Exercise Training.Parry HA, Roberts MD, Kavazis AN. Parry HA, et al. Int J Sports Med. 2020 Jun;41(6):349-359. doi: 10.1055/a-1121-7851. Epub 2020 Mar 11. Int J Sports Med. 2020. PMID: 32162291 Review.
- Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training.Roberts CK, Hevener AL, Barnard RJ. Roberts CK, et al. Compr Physiol. 2013 Jan;3(1):1-58. doi: 10.1002/cphy.c110062. Compr Physiol. 2013. PMID: 23720280 Free PMC article. Review.
- Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle.Bengtsen M, Winje IM, Eftestøl E, Landskron J, Sun C, Nygård K, Domanska D, Millay DP, Meza-Zepeda LA, Gundersen K. Bengtsen M, et al. PLoS Genet. 2021 Nov 9;17(11):e1009907. doi: 10.1371/journal.pgen.1009907. eCollection 2021 Nov. PLoS Genet. 2021. PMID: 34752468 Free PMC article.
- Skeletal Muscle Proteomic Profile Revealed Gender-Related Metabolic Responses in a Diet-Induced Obesity Animal Model.Moriggi M, Belloli S, Barbacini P, Murtaj V, Torretta E, Chaabane L, Canu T, Penati S, Malosio ML, Esposito A, Gelfi C, Moresco RM, Capitanio D. Moriggi M, et al. Int J Mol Sci. 2021 Apr 28;22(9):4680. doi: 10.3390/ijms22094680. Int J Mol Sci. 2021. PMID: 33925229 Free PMC article.
- Weight loss is linearly associated with a reduction of the insulin response to an oral glucose test in Icelandic horses.Delarocque J, Frers F, Huber K, Feige K, Warnken T. Delarocque J, et al. BMC Vet Res. 2020 May 24;16(1):151. doi: 10.1186/s12917-020-02356-w. BMC Vet Res. 2020. PMID: 32448298 Free PMC article.
- Update on the effects of physical activity on insulin sensitivity in humans.Bird SR, Hawley JA. Bird SR, et al. BMJ Open Sport Exerc Med. 2017 Mar 1;2(1):e000143. doi: 10.1136/bmjsem-2016-000143. eCollection 2016. BMJ Open Sport Exerc Med. 2017. PMID: 28879026 Free PMC article. Review.
- Muscle hypertrophy in prediabetic men after 16 wk of resistance training.Stuart CA, Lee ML, South MA, Howell MEA, Stone MH. Stuart CA, et al. J Appl Physiol (1985). 2017 Oct 1;123(4):894-901. doi: 10.1152/japplphysiol.00023.2017. Epub 2017 Jun 29. J Appl Physiol (1985). 2017. PMID: 28663372 Free PMC article.
- Controlled Clinical Trial
- Research Support, N.I.H., Extramural
- Adult
- Bicycling / physiology
- Body Composition
- Body Weight
- Case-Control Studies
- Exercise Therapy*
- Female
- Glucose Transporter Type 4 / metabolism
- Humans
- Insulin
- Insulin Receptor Substrate Proteins / metabolism
- Insulin Resistance*
- Male
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / therapy*
- Middle Aged
- Mitochondrial Proton-Translocating ATPases / metabolism
- Muscle Fibers, Fast-Twitch / cytology
- Muscle Fibers, Fast-Twitch / metabolism
- Muscle Fibers, Slow-Twitch / cytology
- Muscle Fibers, Slow-Twitch / metabolism
- Muscle Strength
- Muscle, Skeletal / cytology*
- Muscle, Skeletal / enzymology
- Muscle, Skeletal / metabolism*
- Oxygen Consumption
- Phosphorylation
- Phosphotransferases (Phosphate Group Acceptor) / metabolism
- Receptor, Insulin / metabolism
- TOR Serine-Threonine Kinases / metabolism
- Young Adult
- Glucose Transporter Type 4
- Insulin
- Insulin Receptor Substrate Proteins
- SLC2A4 protein, human
- MTOR protein, human
- Receptor, Insulin
- TOR Serine-Threonine Kinases
- AMP-dependent kinase (ATP-forming)
- Phosphotransferases (Phosphate Group Acceptor)
- Mitochondrial Proton-Translocating ATPases
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 4. Fiber-specific changes in expression of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3800492/bin/nihms490538f4.jpg)
Figure 5. Cycle training impact on tyrosine…
Figure 5. Cycle training impact on tyrosine and serine phosphorylation of muscle IRS-1
Panels A,…
- Muscle hypertrophy in prediabetic men after 16 wk of resistance training.Stuart CA, Lee ML, South MA, Howell MEA, Stone MH. Stuart CA, et al. J Appl Physiol (1985). 2017 Oct 1;123(4):894-901. doi: 10.1152/japplphysiol.00023.2017. Epub 2017 Jun 29. J Appl Physiol (1985). 2017. PMID: 28663372 Free PMC article.
- Slow-twitch fiber proportion in skeletal muscle correlates with insulin responsiveness.Stuart CA, McCurry MP, Marino A, South MA, Howell ME, Layne AS, Ramsey MW, Stone MH. Stuart CA, et al. J Clin Endocrinol Metab. 2013 May;98(5):2027-36. doi: 10.1210/jc.2012-3876. Epub 2013 Mar 20. J Clin Endocrinol Metab. 2013. PMID: 23515448 Free PMC article.
- Cycle training increased GLUT4 and activation of mammalian target of rapamycin in fast twitch muscle fibers.Stuart CA, Howell ME, Baker JD, Dykes RJ, Duffourc MM, Ramsey MW, Stone MH. Stuart CA, et al. Med Sci Sports Exerc. 2010 Jan;42(1):96-106. doi: 10.1249/MSS.0b013e3181ad7f36. Med Sci Sports Exerc. 2010. PMID: 20010125 Free PMC article.
- Human Skeletal Muscle Mitochondrial Adaptations Following Resistance Exercise Training.Parry HA, Roberts MD, Kavazis AN. Parry HA, et al. Int J Sports Med. 2020 Jun;41(6):349-359. doi: 10.1055/a-1121-7851. Epub 2020 Mar 11. Int J Sports Med. 2020. PMID: 32162291 Review.
- Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training.Roberts CK, Hevener AL, Barnard RJ. Roberts CK, et al. Compr Physiol. 2013 Jan;3(1):1-58. doi: 10.1002/cphy.c110062. Compr Physiol. 2013. PMID: 23720280 Free PMC article. Review.
- Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle.Bengtsen M, Winje IM, Eftestøl E, Landskron J, Sun C, Nygård K, Domanska D, Millay DP, Meza-Zepeda LA, Gundersen K. Bengtsen M, et al. PLoS Genet. 2021 Nov 9;17(11):e1009907. doi: 10.1371/journal.pgen.1009907. eCollection 2021 Nov. PLoS Genet. 2021. PMID: 34752468 Free PMC article.
- Skeletal Muscle Proteomic Profile Revealed Gender-Related Metabolic Responses in a Diet-Induced Obesity Animal Model.Moriggi M, Belloli S, Barbacini P, Murtaj V, Torretta E, Chaabane L, Canu T, Penati S, Malosio ML, Esposito A, Gelfi C, Moresco RM, Capitanio D. Moriggi M, et al. Int J Mol Sci. 2021 Apr 28;22(9):4680. doi: 10.3390/ijms22094680. Int J Mol Sci. 2021. PMID: 33925229 Free PMC article.
- Weight loss is linearly associated with a reduction of the insulin response to an oral glucose test in Icelandic horses.Delarocque J, Frers F, Huber K, Feige K, Warnken T. Delarocque J, et al. BMC Vet Res. 2020 May 24;16(1):151. doi: 10.1186/s12917-020-02356-w. BMC Vet Res. 2020. PMID: 32448298 Free PMC article.
- Update on the effects of physical activity on insulin sensitivity in humans.Bird SR, Hawley JA. Bird SR, et al. BMJ Open Sport Exerc Med. 2017 Mar 1;2(1):e000143. doi: 10.1136/bmjsem-2016-000143. eCollection 2016. BMJ Open Sport Exerc Med. 2017. PMID: 28879026 Free PMC article. Review.
- Muscle hypertrophy in prediabetic men after 16 wk of resistance training.Stuart CA, Lee ML, South MA, Howell MEA, Stone MH. Stuart CA, et al. J Appl Physiol (1985). 2017 Oct 1;123(4):894-901. doi: 10.1152/japplphysiol.00023.2017. Epub 2017 Jun 29. J Appl Physiol (1985). 2017. PMID: 28663372 Free PMC article.
- Controlled Clinical Trial
- Research Support, N.I.H., Extramural
- Adult
- Bicycling / physiology
- Body Composition
- Body Weight
- Case-Control Studies
- Exercise Therapy*
- Female
- Glucose Transporter Type 4 / metabolism
- Humans
- Insulin
- Insulin Receptor Substrate Proteins / metabolism
- Insulin Resistance*
- Male
- Metabolic Syndrome / metabolism*
- Metabolic Syndrome / therapy*
- Middle Aged
- Mitochondrial Proton-Translocating ATPases / metabolism
- Muscle Fibers, Fast-Twitch / cytology
- Muscle Fibers, Fast-Twitch / metabolism
- Muscle Fibers, Slow-Twitch / cytology
- Muscle Fibers, Slow-Twitch / metabolism
- Muscle Strength
- Muscle, Skeletal / cytology*
- Muscle, Skeletal / enzymology
- Muscle, Skeletal / metabolism*
- Oxygen Consumption
- Phosphorylation
- Phosphotransferases (Phosphate Group Acceptor) / metabolism
- Receptor, Insulin / metabolism
- TOR Serine-Threonine Kinases / metabolism
- Young Adult
- Glucose Transporter Type 4
- Insulin
- Insulin Receptor Substrate Proteins
- SLC2A4 protein, human
- MTOR protein, human
- Receptor, Insulin
- TOR Serine-Threonine Kinases
- AMP-dependent kinase (ATP-forming)
- Phosphotransferases (Phosphate Group Acceptor)
- Mitochondrial Proton-Translocating ATPases
- Full Text Sources
- Other Literature Sources
- Medical
- Molecular Biology Databases
- Miscellaneous
![Figure 5. Cycle training impact on tyrosine…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3800492/bin/nihms490538f5.jpg)
Source: PubMed