Keywords
Insulin Resistance
Obesity
Physical Exercise
Glycemia
Skeletal Muscle
Mitochondria
Adipose Tissue
Insulin
Metabolism
Cytokines
Strength Training
How to Cite
Abstract
Background: Currently, the type 2 diabetes mellitus (T2D) is a highly prevalent disease in the world that is characterized by the inability to regulate plasma glucose and involves several phases for its development, including insulin resistance and dysfunction of pancreatic beta cells. The biological mechanisms that lead to the development of the disease involve intracellular alterations in organs such as skeletal muscle, where, triggered by lipotoxicity and glucotoxicity, they condition the development of insulin resistance; and the presence of these same alterations in beta cells that results in reduced insulin production.
Purpose: Understand the biological mechanisms of how exercise prevents aids in the management of type 2 Diabetes Mellitus.
Methodology: Electronic articles from databases from the last ten years as well as Endocrinology and Exercise Physiology text guides in relation to type 2 diabetes mellitus and exercise were reviewed
Results: Both, strength and endurance physical exercise have shown to improve muscle metabolic activity, reduce systemic inflammation, promote mitochondrial function, modify body composition, and contribute to beta cell function. Apparently, part of these effects are secondary to the endocrine action of the muscle, but also to the metabolic and energetic impact that exercise has.
Conclusions: This review demonstrates the biological mechanism in which the exercise is a key pillar for the prevention and treatment of T2DM.
References
Blonde L, Umpierrez GE, McGill JB, Reddy SS, Berga SL, Bush M, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract. 2022 oct;28(10):923-1049. https://doi.org/10.1016/j.eprac.2022.08.002
Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 en.;183:109119. https://doi.org/10.1016/j.diabres.2021.109119
Kirwan JP, Sacks J, Nieuwoudt S. The essential role of exercise in the management of type 2 diabetes. Cleve Clin J Med. 2017 jul. 1;84(7 supl. 1):S15-21. https://doi.org/10.3949/ccjm.84.s1.03
Nery C, De Moraes SR, Novaes KA, Bezerra MA, Silveira PV, Lemos A. Effectiveness of resistance exercise compared to aerobic exercise without insulin therapy in patients with type 2 diabetes mellitus: a meta-analysis. Braz J Phys Ther. 2017 nov. 1;21(6):400-15. https://doi.org/10.1016/j.bjpt.2017.06.004
Karstoft K, Pedersen BK. Exercise and type 2 diabetes: Focus on metabolism and inflammation. Immunol Cell Biol. 2016 febr.;94(2):146-50. https://doi.org/10.1038/icb.2015.101
Fishman SL, Sonmez H, Basman C, Singh V, Poretsky L. The role of advanced glycation end-products in the development of coronary artery disease in patients with and without diabetes mellitus: a review. Mol Med. 2018 nov. 23;24(1):59.
https://doi.org/10.1186/s10020-018-0060-3
Weiss M, Steiner DF, Philipson LH, Feingold K, Anawalt B, Blackman M, et al. Insulin Biosynthesis, Secretion, Structure, and Structure-Activity Relationships. En: Endotext. South Dartmouth, Maryland, Estados Unidos: MDText.com, Inc.; 2000. https://pubmed.ncbi.nlm.nih.gov/25905258/
Henquin JC. Paracrine and autocrine control of insulin secretion in human islets: evidence and pending questions. Am J Physiol Endocrinol Metab. 2021 en. 1;320(1):E78-86. https://doi.org/10.1152/ajpendo.00485.2020
Henquin JC. Non-glucose modulators of insulin secretion in healthy humans: (dis)similarities between islet and in vivo studies. Metabolism. 2021 sept.;122:154821.
https://doi.org/10.1016/j.metabol.2021.154821
Merrins MJ, Corkey BE, Kibbey RG, Prentki M. Metabolic cycles and signals for insulin secretion. Cell Metab. 2022 jul. 5;34(7):947-68. https://doi.org/10.1016/j.cmet.2022.06.003
Tokarz VL, MacDonald PE, Klip A. The cell biology of systemic insulin function. J Cell Biol. 2018 jul. 1;217(7):2273-89. https://doi.org/10.1083/jcb.201802095
Posner BI. Insulin Signalling: The Inside Story. Can J Diabetes. 2017 febr. 1;41(1):108-13. https://doi.org/10.1016/j.jcjd.2016.07.002
Dimitriadis G, Mitron P, Lambadiari V, Maratou E, Raptis SA. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract. 2011 ag.;93(supl. 1):S52-9. https://doi.org/10.1016/S0168-8227(11)70014-6
Smith RL, Soeters MR, Wüst RC, Houtkooper RH. Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease. Endocr Rev. 2018;39(4):489-517. https://doi.org/10.1210/er.2017-00211
Christensen AA, Gannon M. The Beta Cell in Type 2 Diabetes. Curr Diab Rep. 2019;19(9):81. https://doi.org/10.1007/s11892-019-1196-4
Abdul-Ghani MA, Defronzo RA. Pathogenesis of Insulin Resistance in Skeletal Muscle. J Biomed Biotechnol. 2010:476279. https://doi.org/10.1155/2010/476279
Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol. 2019 jun. 1;234(6):8152-61. https://doi.org/10.1002/jcp.27603
Iaccarino G, Franco D, Sorriento D, Strisciuglio T, Barbato E, Morisco C. Modulation of Insulin Sensitivity by Exercise Training: Implications for Cardiovascular Prevention. J Cardiovasc Transl Res. 2021 abr. 1;14(2):256-70. https://doi.org/10.1007/s12265-020-10057-w
Kasuga M. Structure and function of the insulin receptor-a personal perspective. Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(10):581-9. https://doi.org/10.2183/pjab.95.039
Akhtar A, Sah SP. Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer's disease. Neurochem Int. 2020 my.;135:104707.
https://doi.org/10.1016/j.neuint.2020.104707
Ros Pérez M, Medina-Gómez G. Obesity, adipogenesis and insulin resistance. Endocrinol Nutr. 2011;58(7):360-9. https://doi.org/10.1016/j.endoen.2011.05.004
Savage DB, Watson L, Carr K, Adams C, Brage S, Chatterjee KK, et al. Accumulation of saturated intramyocellular lipid is associated with insulin resistance. J Lipid Res. 2019;60(7):1323-32. https://doi.org/10.1194/jlr.M091942
Hammerschmidt P, Brüning JC. Contribution of specific ceramides to obesity-associated metabolic diseases. Cell Mol Life Sci. 2022 ag. 5;79(8):395.
https://doi.org/10.1007/s00018-022-04401-3
Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake Didactic Synopsis Major teaching points. Compr Physiol. 2020;10:785-809.
https://doi.org/10.1002/cphy.c190029
Zhang AM, Wellberg EA, Kopp JL, Johnson JD. Hyperinsulinemia in Obesity, Inflammation, and Cancer. Diabetes Metab J. 2021 my. 1;45(3):285-311.
https://doi.org/10.4093/dmj.2020.0250
Basnet R, Basnet TB, Basnet BB, Khadka S. Overview on thioredoxin-interacting protein (TXNIP): a potential target for diabetes intervention. Curr Drug Targets. 2022 mzo. 4;23(7):761-7. https://doi.org/10.2174/1389450123666220303092324
Mulder H. Transcribing ?-cell mitochondria in health and disease. Mol Metab. 2017 my. 31;6(9):1040-51. https://doi.org/10.1016/j.molmet.2017.05.014
Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal. 2010 febr. 15;12(4):537-77. https://doi.org/10.1089/ars.2009.2531
Usmani-Brown S, Perdigoto AL, Lavoie N, Clark P, Korah M, Rui J, et al. ? cell responses to inflammation. Mol Metab. 2019 sept. 1;27S(supl.):S104-13.
https://doi.org/10.1016/j.molmet.2019.06.013
Wada J, Nakatsuka A. Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes. Acta Med Okayama. 2016;70(3):151-8.
Kwak SH, Park KS, Lee KU, Lee HK. Mitochondrial metabolism and diabetes. J Diabetes Investig. 2010 oct. 19;1(5):161-9. https://doi.org/10.1111/j.2040-1124.2010.00047.x
Creviston T, Quinn L. Exercise and physical activity in the treatment of type 2 diabetes. Nurs Clin North Am. 2001 jun.;36(2):243-71. https://doi.org/10.1016/S0029-6465(22)02547-6
Widmann M, Nieß AM, Munz B. Physical Exercise and Epigenetic Modifications in Skeletal Muscle. Sports Med. 2019 abr.;49(4):509-23. https://doi.org/10.1007/s40279-019-01070-4
Lontchi-Yimagou E, Sobngwi E, Matsha TE, Kengne AP. Diabetes mellitus and inflammation. Curr Diab Rep. 2013 jun.;13(3):435-44. https://doi.org/10.1007/s11892-013-0375-y
Scheffer D da L, Latini A. Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochim Biophys Acta Mol Basis Dis. 2020 oct. 1;1866(10):165823. https://doi.org/10.1016/j.bbadis.2020.165823
Pedersen BK. Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease. Eur J Clin Invest. 2017 ag. 1;47(8):600-11. https://doi.org/10.1111/eci.12781
León-Ariza HH, Mendoza-Navarrete MP, Maldonado-Arango MI, Botero-Rosas DA. A systematic review of “myokines and metabolic regulation”. Apunts Medicina de l'Esport. 2018 oct. 1;53(200):155-62. https://doi.org/10.1016/j.apunts.2018.09.003
Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev. 2006;12:6-33.
León-Ariza HH, Botero-Rosas DA, Acero-Mondragón EJ, Reyes-Cruz D. Soluble interleukin-6 receptor in young adults and its relationship with body composition and autonomic nervous system. Physiol Rep. 2019 dic. 1;7(24):e14315.
https://doi.org/10.14814/phy2.14315
Wedell-Neergaard AS, Lang Lehrskov L, Christensen RH, Legaard GE, Dorph E, Larsen MK, et al. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial. Cell Metab. 2019 abr. 2;29(4):844-55.e3. https://doi.org/10.1016/j.cmet.2018.12.007-6 p
Levelt E, Pavlides M, Banerjee R, Mahmod M, Kelly C, Sellwood J, et al. Ectopic and Visceral Fat Deposition in Lean and Obese Patients With Type 2 Diabetes. J Am Coll Cardiol. 2016 jul. 5;68(1):53-63. https://doi.org/10.1016/j.jacc.2016.03.597
Izzo A, Massimino E, Riccardi G, Della Pepa G. A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors. Nutrients. 2021 en. 1;13(1):1-18. https://doi.org/10.3390/nu13010183
Bajer B, Vlcek M, Galusova A, Imrich R, Penesova A. Exercise associated hormonal signals as powerful determinants of an effective fat mass loss. Endocr Regul. 2015;49(3):151-63. https://doi.org/10.4149/endo_2015_03_151
Gonzalez-Gil AM, Elizondo-Montemayor L. The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review. Nutrients. 2020 jun. 1;12(6):1899. https://doi.org/10.3390/nu12061899
Loimaala A, Groundstroem K, Rinne M, Nenonen A, Huhtala H, Parkkari J, et al. Effect of Long-Term Endurance and Strength Training on Metabolic Control and Arterial Elasticity in Patients With Type 2 Diabetes Mellitus. Am J Cardiol. 2009 abr. 1;103(7):972-7. https://doi.org/10.1016/j.amjcard.2008.12.026
Yang Z, Scott CA, Mao C, Tang J, Farmer AJ. Resistance exercise versus aerobic exercise for type 2 diabetes: A systematic review and meta-analysis. Sports Med. 2014 abr.;44(4):487-99. https://doi.org/10.1007/s40279-013-0128-8
Kanaley JA, Colberg SR, Corcoran MH, Malin SK, Rodriguez NR, Crespo CJ, et al. Exercise/Physical Activity in Individuals with Type 2 Diabetes: A Consensus Statement from the American College of Sports Medicine. Med Sci Sports Exerc. 2022 feb. 1;54(2):353-68. https://doi.org/10.1249/MSS.0000000000002800
Murphy RM, Watt MJ, Febbraio MA. Metabolic communication during exercise. Nat Metab. 2020 sept. 1;2(9):805-16. https://doi.org/10.1038/s42255-020-0258-x
Consitt LA, Dudley C, Saxena G. Impact of Endurance and Resistance Training on Skeletal Muscle Glucose Metabolism in Older Adults. Nutrients. 2019 nov. 1;11(11).
https://doi.org/10.3390/nu11112636
Richter EA. Is GLUT4 translocation the answer to exercise-stimulated muscle glucose uptake? Am J Physiol Endocrinol Metab. 2021 febr. 1;320(2):E240-3.
https://doi.org/10.1152/ajpendo.00503.2020
Zacharewicz E, Hesselink MK, Schrauwen P. Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet quality. J Intern Med. 2018 nov. 1;284(5):505-18. https://doi.org/10.1111/joim.12729
McGarrah RW, Slentz CA, Kraus WE. The Effect of Vigorous- Versus Moderate-Intensity Aerobic Exercise on Insulin Action. Curr Cardiol Rep. 2016 dic.;18(12):117. https://doi.org/10.1007/s11886-016-0797-7
De Sousa RA, Improta-Caria AC, Cassilhas RC. Effects of physical exercise on memory in type 2 diabetes: a brief review. Metab Brain Dis. 2021;36:1559-63. https://doi.org/10.1007/s11011-021-00752-1
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