The Effect of Various Training on the Expression of the 5’amp-Activated Protein Kinase Α2 and Glucose Transporter - 4 in Type-2 Diabetes Mellitus Rat

Authors

  • Rahmi Rahmi Department of Biomedical Sciences, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
  • Yetty Machrina Department of Physiology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0003-0635-8436
  • Zulham Yamamoto Department of Histology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2022.7913

Keywords:

Aerobic training, AMPK, Type 2 diabetes mellitus

Abstract

BACKGROUND: Exercise is the main pillar in Type 2 Diabetes Mellitus (T2DM) management. The mechanism of glucose uptake mediated by exercise is different from insulin, and this mechanism is not disturbed in T2DM. One of the mechanisms is through the activation of 5’AMP-activated protein kinase (AMPK). AMPK also regulates the glucose transporter 4 (GLUT4) expression. Effect various types of exercise to AMPK α2 and GLUT-4 of the skeletal muscle still limited.

AIM: This study aims to determine the effect of various physical training on the expression of Ampk α2 and Glut 4 in skeletal muscle of T2DM rats.

METHODS: This study used stored skeletal muscles of 25 T2DM Wistar rats. Previously, the rats were divided into groups of K1 (control, not given exercise), K2 (moderate continuous training), K3 (severe continuous training), K4 (slow interval training), and K5 (fast interval training). Running on a treadmill frequency 3 times a week for 8 weeks. The relative expression of Ampk α2 and Glut 4 were assessed using Real Time-PCR and were compared among the groups using the Livak formula.

RESULTS: Moderate intensity continuous training increased Ampk α2 and Glut 4 expression by 1.45 and 2.39 times, respectively. Severe intensity continuous training increased the expression of Ampk α2 and Glut 4 by 1.55 and 2.56 times, respectively. Slow interval training increased the expression of Ampk α2 and Glut 4 by 4.41 and 3.76 times, respectively. The expression of Ampk α2 and Glut4 in fast interval training was 4.56 and 4.79 times more than control.

CONCLUSION: Continuous and interval training increase Ampk α2 and Glut 4 expression. The fast interval training showed the highest expression of Ampk α2 and Glut 4.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. https://doi.org/10.1016/j.diabres.2019.107843 PMid:31518657 DOI: https://doi.org/10.1016/j.diabres.2019.107843

Ditjen Kesehatan Masyarakat Kementrian Kesehatan. Kementrian Kesehatan Republik Indonesia, Hasil Riskesdas Tahun 2018; 2020. Available from: https://www.kesmas.kemkes.go.id/assets/upload/dir_519d41d8cd98f00/files/Hasilriskesdas-2018_1274.pdf [Last accessed on 2020 Nov 20].

Neill HM. AMPK and exercise: Glucose uptake and insulin sensitivity. Diabetes Metab J. 2013;37(1):1-21. https://doi.org/10.4093/dmj.2013.37.1.1 PMid:23441028 DOI: https://doi.org/10.4093/dmj.2013.37.1.1

Sharabi K, Tavares CD, Rines AK, Puigserver P. Molecular pathophysiology of hepatic glucose production. Mol Aspects Med. 2015;46:21-33. https://doi.org/10.1016/j.mam.2015.09.003 PMid:26549348 DOI: https://doi.org/10.1016/j.mam.2015.09.003

PERKENI. In: Soelistijo SA, Novida H, editors. Konsensus Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia 2015. Jakarta: PB PERKENI; 2015. p. 10-61.

Richter EA, Hargreaves M. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993-1017. PMid:23899560 DOI: https://doi.org/10.1152/physrev.00038.2012

Stanford KI, Goodyear LJ. Exercise and Type 2 diabetes: Molecular mechanisms regulating glucose uptake in skeletal muscle. Adv Physiol Educ. 2014;38:308-14. https://doi.org/10.1152/advan.00080.2014 PMid:25434013 DOI: https://doi.org/10.1152/advan.00080.2014

Yan Y, Zhou XE, Xu HE, Melcher K. Structure and physiological regulation of AMPK. Int J Mol Sci. 2018;19(11):3534. https://doi.org/10.3390/ijms19113534 PMid:30423971 DOI: https://doi.org/10.3390/ijms19113534

Richter EA, Ruderman NB. AMPK and the biochemistry of exercise: Implications for human health and disease. Biochem J. 2010;418(2):261-75. https://doi.org/10.1042/BJ20082055 PMid:19196246 DOI: https://doi.org/10.1042/BJ20082055

Pereira RM, Sanchez A. Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise. Moritz Rio Carlo. 2017;23:1-8. DOI: https://doi.org/10.1590/s1980-6574201700si0004

Mcgee SL, van Denderen BJ, Howlett KF, Mollica J, Schertzer JD, Kemp BE, et al. AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Clin Exp Pharmacol Physiol. 2008;57:860-7. DOI: https://doi.org/10.2337/db07-0843

Hussey SE, McGee SL, Garnham A, Wentworth JM, Jeukendrup AE, Hargreaves M. Research letter in patients with Type 2 diabetes research letter. Diabetes Obes Metab. 2011;13(10):959-62. https://doi.org/10.1111/j.1463-1326.2011.01426.x PMid:21615668 DOI: https://doi.org/10.1111/j.1463-1326.2011.01426.x

Cao S, Li B, Yi X, Chang B, Zhu B, Lian Z, et al. Effects of exercise on AMPK signaling and downstream components to PI3K in rat with Type 2 diabetes. PLoS One. 2012;7(12):e51709. https://doi.org/10.1371/journal.pone.0051709 PMid:23272147 DOI: https://doi.org/10.1371/journal.pone.0051709

Hansen JS, Zhao X, Irmler M, Liu X, Hoene M, Scheler M, et al. Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery. Diabetologia. 2015;58(8):1845-54. DOI: https://doi.org/10.1007/s00125-015-3584-x

Lantier L, Fentz J, Mounier R, Leclerc J, Treebak JT, Pehmøller C, et al. AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity. FASEB J. 2014;28(7):3211-24. https://doi.org/10.1096/fj.14-250449 PMid:24652947 DOI: https://doi.org/10.1096/fj.14-250449

Jørgensen SB, Jensen TE, Richter EA. Role of AMPK in skeletal muscle gene adaptation in relation to exercise. Appl Physiol Nutr Metab. 2007;32(5):904-11. https://doi.org/10.1139/H07-079 PMid:18059615 DOI: https://doi.org/10.1139/H07-079

Gong H, Xie J, Zhang N, Yao L, Zhang Y. MEF2A binding to the Glut4 promoter occurs via an AMPKα 2-dependent mechanism. Med Sci Sports Exerc. 2011;43(8):1441-50. https://doi.org/10.1249/MSS.0b013e31820f6093 PMid:21233771 DOI: https://doi.org/10.1249/MSS.0b013e31820f6093

Francois ME, Little JP. Effectiveness and safety of high-intensity interval training in patients with Type 2 diabetes. Diabetes Spectr. 2015;28(1):39-44. https://doi.org/10.2337/diaspect.28.1.39 PMid:25717277 DOI: https://doi.org/10.2337/diaspect.28.1.39

American Diabetes Association. Lifestyle Management: Standards of Medical Care in Diabetes 2019. Diabetes Care. 2019;42:46-60. DOI: https://doi.org/10.2337/dc19-S005

Spanoudaki S. Interval versus continuous training. J Sports Med Doping Stud. 2011;1(1):4172. DOI: https://doi.org/10.4172/2161-0673.1000e102

Mitranun W, Deerochanawong C, Tanaka H, Suksom D. Continuous vs interval training on glycemic control and macro- and microvascular reactivity in Type 2 diabetic patients. Scand J Med Sci Sport. 2014;24(2):69-76. https://doi.org/10.1111/sms.12112 PMid:24102912 DOI: https://doi.org/10.1111/sms.12112

Álvarez C, Ramirez-campillo R, Alvarez C, Mancilla R, Ciolac EG. Low-volume high-intensity interval training as a therapy for Type 2 diabetes. Int J Sport Med. 2016;3:1-8. https://doi.org/10.1055/s-0042-104935 PMid:27259099 DOI: https://doi.org/10.1055/s-0042-104935

De Nardi AT, Tolves T, Lenzi TL, Signori LU, da Silva AM. High-intensity interval training versus continuous training on physiological and metabolic variables in prediabetes and Type 2 diabetes: A meta-analysis. Diabetes Res Clin Pract. 2018;137:149-59. https://doi.org/10.1016/j.diabres.2017.12.017 PMid:29329778 DOI: https://doi.org/10.1016/j.diabres.2017.12.017

Machrina Y, Damanik HA, Purba A, Lindarto D. Effect various type of exercise to Insr gene expression, skeletal muscle insulin receptor and insulin resistance on diabetes mellitus type-2 model rats. Int J Health Sci. 2018;6(4):50-6.

Zhang M, Lv XY, Li J, Xu ZG, Chen L. The characterization of high-fat diet and multiple low-dose streptozotocin induced Type 2 diabetes rat model. Exp Diabetes Res. 2008;2008:704045. https://doi.org/10.1155/2008/70404 PMid:19132099 DOI: https://doi.org/10.1155/2008/704045

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402-8. https://doi.org/10.1006/meth.2001.1262 PMid:11846609 DOI: https://doi.org/10.1006/meth.2001.1262

Brandt N, de Bock K, Richter EA, Hespel P. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats. Am J Physiol Endocrinol Metab. 2010;299(2):E215-24. https://doi.org/10.1152/ajpendo.00098.2010 PMid:20484011 DOI: https://doi.org/10.1152/ajpendo.00098.2010

Carling D, Mayer FV, Sanders MJ, Gamblin SJ. AMPK-activated protein kinase: Nature’s energy sensor. Nat Chem Biol. 2011;7(8):512-8. https://doi.org/10.1038/nchembio.610 PMid:21769098 DOI: https://doi.org/10.1038/nchembio.610

Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, et al. Activation of AMP-activated protein kinase in the liver: A new strategy for the management of metabolic hepatic disorders. J Physiol. 2006;574(1):41-53. DOI: https://doi.org/10.1113/jphysiol.2006.108506

Machrina Y, Pane YS, Lindarto D. The expression of liver metabolic enzymes ampkα1, ampkα2, and pgc-1α due to exercise in Type-2 diabetes mellitus rat model. Open Access Maced J Med Sci. 2020;8:629-32. DOI: https://doi.org/10.3889/oamjms.2020.4550

Thomson DM. The role of AMPK in the regulation of skeletal muscle size, hypertrophy, and regeneration. Int J Mol Sci. 2018;19(10):3125. https://doi.org/10.3390/ijms19103125 PMid:30314396 DOI: https://doi.org/10.3390/ijms19103125

Torma F, Gombos Z, Jokai M, Takeda M, Mimura T, Radak Z. High intensity interval training and molecular adaptive response of skeletal muscle. Sport Med Health Sci. 2019;1(1):24-32. DOI: https://doi.org/10.1016/j.smhs.2019.08.003

Combes A, Dekerle J, Webborn N, Watt P, Bougault V, Daussin FN. Exercise-induced metabolic fluctuations influence AMPK, p38-MAPK and CaMKII phosphorylation in human skeletal muscle. Physiol Rep. 2015;3(9):e12462. https://doi.org/10.14814/phy2.12462 PMid:26359238 DOI: https://doi.org/10.14814/phy2.12462

DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in Type 2 diabetes. Diabetes Care. 2009;32 Suppl 2:S157-63. https://doi.org/10.2337/dc09-S302 PMid:19875544 DOI: https://doi.org/10.2337/dc09-S302

Gutierrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: An update. Gac Med Mex. 2017;153:197-209. PMid:28474708

Lehnen AM. Changes in the GLUT4 expression by acute exercise, exercise training and detraining in experimental models. J Diabetes Metab. 2013;1(10):1-8. DOI: https://doi.org/10.4172/2155-6156.S10-002

Ojuka EO, Goyaram V, Smith JA. The role of CaMKII in regulating GLUT4 expression in skeletal muscle. Am J Physiol Endocrinol Metab. 2012;303(3):322-31. https://doi.org/10.1152/ajpendo.00091.2012 PMid:22496345 DOI: https://doi.org/10.1152/ajpendo.00091.2012

Ling C, Roon T, Nitert MD. Epigenetics and Type-2 Diabetes in Epigenetics Aspect of Chronic Diseases. Berlin, Germany: Springer; 2011. p. 135-45. DOI: https://doi.org/10.1007/978-1-84882-644-1_9

Koh JH, Hancock CR, Han DH, Holloszy JO, Nair KS, Dasari S. AMPK and PPARβ positive feedback loop regulates endurance exercise training-mediated GLUT4 expression in skeletal muscle. Am J Physiol Endocrinol Metab. 2019;316(5):E931-9. https://doi.org/10.1152/ajpendo.00460.2018 PMid:30888859 DOI: https://doi.org/10.1152/ajpendo.00460.2018

Machrina Y, Purba A, Lindarto D, Maskoen AM. Exercise intensity alter insulin receptor gene expression in diabetic Type-2 rat model. Open Access Maced J Med Sci. 2019;7(20):3370-5. https://doi.org/10.3889/oamjms.2019.425 PMid:32002053 DOI: https://doi.org/10.3889/oamjms.2019.425

Downloads

Published

2022-01-28

How to Cite

1.
Rahmi R, Machrina Y, Yamamoto Z. The Effect of Various Training on the Expression of the 5’amp-Activated Protein Kinase Α2 and Glucose Transporter - 4 in Type-2 Diabetes Mellitus Rat. Open Access Maced J Med Sci [Internet]. 2022 Jan. 28 [cited 2024 Apr. 18];10(A):1-5. Available from: https://oamjms.eu/index.php/mjms/article/view/7913

Issue

Section

Sports Medicine

Categories