Skeletal muscle has an important role in the
pathogenesis of insulin resistance. Several studies have found that insulin
action may be related to the oxidative capacity of skeletal muscle. Aerobic
exercises improve both insulin sensitivity and activity of oxidative enzymes in
muscle. Individuals having disorders and diseases like insulin resistance, obesity
or type 2 diabetes were found to have lower muscle oxidative enzyme activity. Some
hypotheses have been developed regarding the hypothesis that insulin infusion
stimulates the mitochondrial protein synthesis rate in skeletal muscle. The effects
of exercise on mitochondrial dysfunction and insulin sensitivity are summarized
and discussed in this review.
Affourtit, C. (2016). Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics. Biochimica et biophysica acta; 1857(10):1678-1693.
Boulinguiez, A., Staels, B., Duez, H., & Lancel, S. Mitochondria and endoplasmic reticulum: Targets for a better insulin sensitivity in skeletal muscle? Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2017; 1862(9):901-16.
Cheng, A., Dube, N., Gu, F., & Tremblay, M.L. (2002). Coordinated action of protein tyrosine phosphatases in insulin signal transduction. European Journal of Biochemistry, 269: 1050–1059.
Costa, C.G., Guerand, E.S., Struys, E.A., Holwerda, U., Ten Brink, H.J., Tavares de Almeida, I. ve diğerleri. (2000) Quantitative analysis of urinary acylglycines for the diagnosis of β oxidation defects using GC- NCI- MS. Journal of Pharmaceutical and Biomedical Analysis, 21: 1215- 1224.
Cree-Green, M., Newcomer, B.R., Brown, M.S., Baumgartner, A.D., Bergman, B., Drew, B., ve diğerleri. (2015). Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes, 64(2):383-392.
Davidson, L.E., Hudson, R., Klipatrick, K., Kuk, J.L., McMillan, K., Janiszewski, P.M. ve diğerleri. (2009). Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial. Archieves of Internal Medicine, 169: 122- 131.
Fealy, C.E., Mulya, A., Lai, N.,& Kirwan, J.P. (2014). Exercise training decreases activation of the mitochondrial fission protein dynamin-related protein-1 in insulin-resistant human skeletal muscle. Journal of Applied Physiology, 117(3):239-245.
Finaud, J., Lac, G., & Filaire, E. (2006).Oxidative stress: relationship with exercise and training. Sports Medicine, 36: 427- 358.
Garber, C.E., Blissmer, B., Deschenes, M.R., Franklin, B.A., LLamonte, M.J., Lee, I.M., Nieman, D.C., &Swain, D.P. (2011). American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculosketal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Medicine and Science in Sports and Exercise, 43: 1334- 1359.
Holloszy, J.O. (2009). Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance. The American journal of clinical nutrition, 89(1):463-466.
Huffman, K.M., Shah, S.H., Steverns, R.D., Bain, J.R., Muehlbauer, M., Slentz, C.A. ve diğerleri. (2009). Relationships between circulating metabolic intermediates and insulin action in overweight to obese inactive men and women. Diabetes Care, 32: 1678- 1683.
Huffman, K.M., Slentz, C.A., Bateman, L.A., Thompson, D., Muehlbauer, M.J., Bain, J.R. ve diğerleri. (2011). Exercise- induced changes in metabolic ıntermediates, hormones, and ınflammatory markers associated with improvements in insulin sensitivity. Diabetes Care, 34: 174- 176.
Kelley, D.E., He, J., Menshikova, E.V., & Ritov, V.B. (2002). Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes, 51: 2944–2950.
Kim, J., Wei, Y., Sowers, J.R. (2008). Role of mitochondrial dysfunction in ınsulin resistance. Circulation Research, 102(4): 401- 414.
Koves, T.R., Li, P., An, J., Akimoto, T., Slentz, D., Ilkayeva, O. ve diğerleri (2005). Peroxisome proliferator- activated receptor- γ co- activator 1α- mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid- induced mitochondrial inefficiency. Journal of Biological Chemistry, 280: 33588- 33598.
Lanza, I.R., Short, D.K., Short, K.R., Raghavakaimal, S., Basu, R., JJoyner, M.J. ve diğerleri. (2008). Endurance exercise as a countermeasure for aging. Diabetes, 57: 2955- 2942.
Margolis, L.M., & Pasiakos, S.M. (2013). Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis. Advances in nutrition (Bethesda, Md), 4(6):657-64.
McCormack, S.E., McCarthy, M.A., Harrington, S.G., Farilla, L., Hrovat, M.I., Systrom, D.M. ve diğerleri. (2014). Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents. Pediatric obesity, 9(4):281-291.
Nisoli, E., Clementi, E., Carruba, M.O., & Moncada, S. (2007). Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome? Circulation Research, 100: 795- 806.
Parise, G., Brose, A.N., &Tarnopolsky, M.A. (2005). Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Experimental Gerontology, 40: 173- 180.
Patti, M.E., Butte, A.J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S. ve diğerleri. (2003). Coordinated reduction of genes of oxidative metabolism in humans with insülin resistance and diabetes: Potential role of PGC1 and NRF1. Proceedings of the National Academy of Sciences, 100: 8466- 8471.
Peterson, C.M., Johannsen, D.L., & Ravussin E. (2012). Skeletal muscle mitochondria and aging: a review. Journal of Aging Research, 21: 1948- 2021.
Schrauwen-Hinderling, V.B., Kooi, M.E., &Schrauwen, P. (2016). Mitochondrial Function and Diabetes: Consequences for Skeletal and Cardiac Muscle Metabolism. Antioxidants & redox signaling, 24(1):39-51.
Sherratt, H.S., &Turnbull, D.M. (1990). Mitochondrial oxidations and ATP synthesis in muscle. Baillière's Clinical Endocrinology and Metabolism, 4: 523- 560.
Strump, C.S., Short, K.R., Bigelow, M.L., Schimke, J.M., & Nair, K.S. (2003). Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proceedings of the National Academy of Sciences, 100(13): 7996- 8001.
Summermatter, S., Shui, G., Maag, D., Santos, G., Wenk, M.R., &Handschin, C. (2013). PGC- 1alpha improves glucose homeostasis in skeletal muscle in an activity- dependent manner. Diabetes, 62: 85- 95.
Szendroedi, J., Phielix, E., &Roden, M. (2011). The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nature Reviews Endocrinology, 8: 92- 103.
Trevellin, E., Scorzeto, M., Olivieri, M., Granzotto, M., Valerio, A., Tedesco, L. ve diğerleri. (2014). Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes, 63(8):2800-2811.
Warburton, D.E., Nicol, C.W., &Bredin, S.S. (2006). Health benefits of physical activity: the evidence. CMAJ, 174: 801- 809.
Weibel, E.R., &Hoppeler, H. (2005). Exercise- induced maximal metabolic rate scales with muscle aerobic capacity. Journal of Experimental Biology, 208: 1635- 1644.
Zhang, H.H., Ma, X.J., Wu, L.N., Zhao, Y.Y., Zhang, P.Y., Zhang, Y.H. ve diğerleri. (2015). SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells. Experimental Biology and Medicine, 240(5):557-565.
Egzersiz, İnsülin Duyarlılığı ve Mitokondriyal Fonksiyonu Etkiler Mi?
İskelet kası
insülin direnci patogenezinde önemli rol oynamaktadır. Yapılan çalışmalarda,
vücuttaki insülin hareketlerinin iskelet kası oksidatif kapasitesi ile ilişkili
olabileceği bulunmuştur. Aerobik egzersizler hem insülin duyarlılığı hem de kas
oksidatif enzim aktivitesini arttırmaktadır. Kas oksidatif enzim aktivitesinin obezite,
insülin direnci veya tip 2 diyabet gibi kronik hastalıkları olan bireylerde daha
düşük olduğu saptanmıştır. İnsülin infüzyonunun iskelet kasındaki mitokondriyal
protein sentez hızını da uyardığıyla ilgili hipotezler bulunmaktadır. Bu
derlemede, egzersizin mitokondriyal disfonksiyon ve insülin duyarlılığı üzerine
etkisini araştıran yayınları değerlendirilerek özetlenmiştir.
Affourtit, C. (2016). Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics. Biochimica et biophysica acta; 1857(10):1678-1693.
Boulinguiez, A., Staels, B., Duez, H., & Lancel, S. Mitochondria and endoplasmic reticulum: Targets for a better insulin sensitivity in skeletal muscle? Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2017; 1862(9):901-16.
Cheng, A., Dube, N., Gu, F., & Tremblay, M.L. (2002). Coordinated action of protein tyrosine phosphatases in insulin signal transduction. European Journal of Biochemistry, 269: 1050–1059.
Costa, C.G., Guerand, E.S., Struys, E.A., Holwerda, U., Ten Brink, H.J., Tavares de Almeida, I. ve diğerleri. (2000) Quantitative analysis of urinary acylglycines for the diagnosis of β oxidation defects using GC- NCI- MS. Journal of Pharmaceutical and Biomedical Analysis, 21: 1215- 1224.
Cree-Green, M., Newcomer, B.R., Brown, M.S., Baumgartner, A.D., Bergman, B., Drew, B., ve diğerleri. (2015). Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes, 64(2):383-392.
Davidson, L.E., Hudson, R., Klipatrick, K., Kuk, J.L., McMillan, K., Janiszewski, P.M. ve diğerleri. (2009). Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial. Archieves of Internal Medicine, 169: 122- 131.
Fealy, C.E., Mulya, A., Lai, N.,& Kirwan, J.P. (2014). Exercise training decreases activation of the mitochondrial fission protein dynamin-related protein-1 in insulin-resistant human skeletal muscle. Journal of Applied Physiology, 117(3):239-245.
Finaud, J., Lac, G., & Filaire, E. (2006).Oxidative stress: relationship with exercise and training. Sports Medicine, 36: 427- 358.
Garber, C.E., Blissmer, B., Deschenes, M.R., Franklin, B.A., LLamonte, M.J., Lee, I.M., Nieman, D.C., &Swain, D.P. (2011). American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculosketal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Medicine and Science in Sports and Exercise, 43: 1334- 1359.
Holloszy, J.O. (2009). Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance. The American journal of clinical nutrition, 89(1):463-466.
Huffman, K.M., Shah, S.H., Steverns, R.D., Bain, J.R., Muehlbauer, M., Slentz, C.A. ve diğerleri. (2009). Relationships between circulating metabolic intermediates and insulin action in overweight to obese inactive men and women. Diabetes Care, 32: 1678- 1683.
Huffman, K.M., Slentz, C.A., Bateman, L.A., Thompson, D., Muehlbauer, M.J., Bain, J.R. ve diğerleri. (2011). Exercise- induced changes in metabolic ıntermediates, hormones, and ınflammatory markers associated with improvements in insulin sensitivity. Diabetes Care, 34: 174- 176.
Kelley, D.E., He, J., Menshikova, E.V., & Ritov, V.B. (2002). Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes, 51: 2944–2950.
Kim, J., Wei, Y., Sowers, J.R. (2008). Role of mitochondrial dysfunction in ınsulin resistance. Circulation Research, 102(4): 401- 414.
Koves, T.R., Li, P., An, J., Akimoto, T., Slentz, D., Ilkayeva, O. ve diğerleri (2005). Peroxisome proliferator- activated receptor- γ co- activator 1α- mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid- induced mitochondrial inefficiency. Journal of Biological Chemistry, 280: 33588- 33598.
Lanza, I.R., Short, D.K., Short, K.R., Raghavakaimal, S., Basu, R., JJoyner, M.J. ve diğerleri. (2008). Endurance exercise as a countermeasure for aging. Diabetes, 57: 2955- 2942.
Margolis, L.M., & Pasiakos, S.M. (2013). Optimizing intramuscular adaptations to aerobic exercise: effects of carbohydrate restriction and protein supplementation on mitochondrial biogenesis. Advances in nutrition (Bethesda, Md), 4(6):657-64.
McCormack, S.E., McCarthy, M.A., Harrington, S.G., Farilla, L., Hrovat, M.I., Systrom, D.M. ve diğerleri. (2014). Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents. Pediatric obesity, 9(4):281-291.
Nisoli, E., Clementi, E., Carruba, M.O., & Moncada, S. (2007). Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome? Circulation Research, 100: 795- 806.
Parise, G., Brose, A.N., &Tarnopolsky, M.A. (2005). Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Experimental Gerontology, 40: 173- 180.
Patti, M.E., Butte, A.J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S. ve diğerleri. (2003). Coordinated reduction of genes of oxidative metabolism in humans with insülin resistance and diabetes: Potential role of PGC1 and NRF1. Proceedings of the National Academy of Sciences, 100: 8466- 8471.
Peterson, C.M., Johannsen, D.L., & Ravussin E. (2012). Skeletal muscle mitochondria and aging: a review. Journal of Aging Research, 21: 1948- 2021.
Schrauwen-Hinderling, V.B., Kooi, M.E., &Schrauwen, P. (2016). Mitochondrial Function and Diabetes: Consequences for Skeletal and Cardiac Muscle Metabolism. Antioxidants & redox signaling, 24(1):39-51.
Sherratt, H.S., &Turnbull, D.M. (1990). Mitochondrial oxidations and ATP synthesis in muscle. Baillière's Clinical Endocrinology and Metabolism, 4: 523- 560.
Strump, C.S., Short, K.R., Bigelow, M.L., Schimke, J.M., & Nair, K.S. (2003). Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proceedings of the National Academy of Sciences, 100(13): 7996- 8001.
Summermatter, S., Shui, G., Maag, D., Santos, G., Wenk, M.R., &Handschin, C. (2013). PGC- 1alpha improves glucose homeostasis in skeletal muscle in an activity- dependent manner. Diabetes, 62: 85- 95.
Szendroedi, J., Phielix, E., &Roden, M. (2011). The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nature Reviews Endocrinology, 8: 92- 103.
Trevellin, E., Scorzeto, M., Olivieri, M., Granzotto, M., Valerio, A., Tedesco, L. ve diğerleri. (2014). Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes, 63(8):2800-2811.
Warburton, D.E., Nicol, C.W., &Bredin, S.S. (2006). Health benefits of physical activity: the evidence. CMAJ, 174: 801- 809.
Weibel, E.R., &Hoppeler, H. (2005). Exercise- induced maximal metabolic rate scales with muscle aerobic capacity. Journal of Experimental Biology, 208: 1635- 1644.
Zhang, H.H., Ma, X.J., Wu, L.N., Zhao, Y.Y., Zhang, P.Y., Zhang, Y.H. ve diğerleri. (2015). SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells. Experimental Biology and Medicine, 240(5):557-565.
Devrim, A., & Bilgiç, P. (2017). Does Exercise Effect on Mitochondrial Dysfunction and Insulin Sensitivity?. Hacettepe University Faculty of Health Sciences Journal, 4(3), 31-37. https://doi.org/10.21020/husbfd.341817