The Pattern of Peroxisome Proliferator-activated Receptor Gamma Coactivator 1-alpha Gene Expression in Type-2 Diabetes Mellitus Rat Model Liver: Focus on Exercise

Yetty Machrina; Dharma Lindarto; Yunita Sari Pane; Novita Sari Harahap

doi:10.3889/oamjms.2021.6362

Authors

Yetty Machrina Departement of Physiology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
Dharma Lindarto Departement of Internal Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
Yunita Sari Pane Departement of Pharmacology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0001-5638-4734
Novita Sari Harahap Departement of Sport Medicine, Faculty of Sport Medicine, Universitas Negeri, Medan, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.6362

Keywords:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, Liver, Type-2 diabetes mellitus, Rat, Exercise

Abstract

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has an important role in mitochondria biogenesis which generated cellular metabolism. Carbohydrate metabolism in the liver is crucial to maintain plasma blood glucose.

AIM: This research aimed to determine the expression of PGC-1α gene in the liver type-2 diabetes mellitus (T2DM) rat model, after treatment with a focus on exercise.

METHODS: We used 25 healthy male Wistar rats as subjects. Rats were modified to T2DM models by feeding a high-fat diet and low-dose streptozotocin injection. We divided the rats into five groups, that is, sedentary group as a control and four others as treatment groups. The exercise was assigned for treatment groups by a run on the treadmill as moderate intensity continuous (MIC), highintensity continuous (HIC), slow interval (SI), and fast interval (FI). The treatment groups were exercise throughout 8 weeks with a frequency of 3 times a week.

RESULTS: The results showed that expression of PGC-1α gene was lower in all treatment groups compared to controls (p < 0.05). Expression in HIC was higher than MIC (p < 0.05), so was the expression in FI more than SI (p < 0.05).

CONCLUSIONS: Exercise affected PGC-1α gene expression in the liver of the T2DM rat model. The expression of PGC-1α was linear with exercise intensity.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Soewondo P, Ferrario A, Tahapary DL. Challenges in diabetes management in Indonesia: A literature review. Global Health. 2013;9(1):63. https://doi.org/10.1186/1744-8603-9-63 PMid:24299164 DOI: https://doi.org/10.1186/1744-8603-9-63

Indonesian Ministry of Health. Laporan Nasional Riset Kesehatan Dasar 2018. The Indonesian Ministry of Health’s National Research and Development Agency; 2019. Available from: http://www.labmandat.litbang.depkes.go.id/images/download/laporan/rkd/2018/laporan_nasional_rkd2018_final.pdf. https://doi.org/10.17501/24246735.2018.4105 DOI: https://doi.org/10.17501/24246735.2018.4105

Liang H, Ward WF. PGC-1α: A key regulator of energy metabolism. Adv Physiol Educ. 2006;30(4):145-51. PMid:17108241 DOI: https://doi.org/10.1152/advan.00052.2006

Finck BN, Kelly DP. PGC-1 coactivators: Inducible regulators of energy metabolism in health and disease. J Clin Invest. 2006;116(3):615-22. https://doi.org/10.1172/jci27794 PMid:16511594 DOI: https://doi.org/10.1172/JCI27794

Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator. Endocr Rev. 2003;24(1):78-90. https://doi.org/10.1210/er.2002-0012 PMid:12588810 DOI: https://doi.org/10.1210/er.2002-0012

Setyawati T. Peroxisome proliferator activated receptor-γ (Ppar-γ) coactivator 1-α (PGC-1 α) in type 2 Diabetes Mellitus and its role in mitochondrial function. Med Tadulako. 2014;1(1):54-62.

Corona JC, Duchen MR. PPAR gamma and PGC-1alpha as therapeutic targets in Parkinson’s. Neurochem Res. 2015;40(2):308-16. PMid:25007880 DOI: https://doi.org/10.1007/s11064-014-1377-0

Wu H, Deng X, Shi Y, Su Y, Wei J, Duan H. PGC-1α, glucose metabolism and Type 2 diabetes mellitus. J Endocrinol. 2016;229(3):R99-115. https://doi.org/10.1530/joe-16-0021 PMid:27094040 DOI: https://doi.org/10.1530/JOE-16-0021

Sugden MI, Caton PW, Holness MJ. PPAR control: It’s SIRTainly as easy as PGC. J Endocrinol. 2010;204(2):93-104. https://doi.org/10.1677/joe-09-0359 PMid:19770177 DOI: https://doi.org/10.1677/JOE-09-0359

Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008;102(4):401-14. PMid:18309108 DOI: https://doi.org/10.1161/CIRCRESAHA.107.165472

Łukaszuk B, Kurek K, Mikłosz A, Żendzian-Piotrowska M, Chabowski A. The role of PGC-1α in the development of insulin resistance in skeletal muscle-revisited. Cell Physiol Biochem. 2015;37(6):2288-96. https://doi.org/10.1159/000438584 PMid:26625097 DOI: https://doi.org/10.1159/000438584

Li N, Brun T, Cnop M, Cunha DA, Eizirik DL, Maechler P. Transient oxidative stress damages mitochondrial machinery inducing persistent beta-cell dysfunction. J Biol Chem. 2009;284(35):23602-12. https://doi.org/10.1074/jbc.m109.024323 PMid:19546218 DOI: https://doi.org/10.1074/jbc.M109.024323

Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267-73. https://doi.org/10.1038/ng1180 PMid:12808457 DOI: https://doi.org/10.1038/ng1180

Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad HICi USA. 2003;100(14):8466-71. https://doi.org/10.1073/pnas.1032913100 PMid:12832613 DOI: https://doi.org/10.1073/pnas.1032913100

Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92(6):829-39. https://doi.org/10.1016/s0092-8674(00)81410-5 DOI: https://doi.org/10.1016/S0092-8674(00)81410-5

Leick L, Fentz J, Biensø RS, Knudsen JG, Jeppesen J, Kiens B, et al. PGC-1α is required for AICAR-induced expression of GLUT4 and mitochondrial proteins in mouse skeletal muHICle. Am J Physiol Endocrinol Metab. 2010;299(3):E456-65. https://doi.org/10.1152/ajpendo.00648.2009 PMid:20628026 DOI: https://doi.org/10.1152/ajpendo.00648.2009

Safdar A, Little JP, Stokl AJ, Hettinga BP, Akhtar M, Tarnopolsky MA. Exercise increases mitochondrial PGC-1α content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J Biol Chem. 2011;286(12):10605-17. https://doi.org/10.1074/jbc.m110.211466 PMid:21245132 DOI: https://doi.org/10.1074/jbc.M110.211466

Buler M, Aatsinki SM, Skoumal R, Komka Z, To M, Kerkela R, et al. Energy-sensing factors coactivator peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α) and AMP-activated protein kinase control expression of inflammatory mediators in liver induction of interleukin 1 receptor antagonist. J Biol Chem. 2012;287(3):1847-60. https://doi.org/10.1074/jbc.m111.302356 PMid:22117073 DOI: https://doi.org/10.1074/jbc.M111.302356

Huang AM, Jen CJ, Chen HF, Yu L, Kuo YM, Chen HI. Compulsive exercise acutely upregulates rat hippocampal brain-derived neurotrophic factor. J Neural Transm (Vienna). 2006;113(7):803-11. https://doi.org/10.1007/s00702-005-0359-4 PMid:16252072 DOI: https://doi.org/10.1007/s00702-005-0359-4

Kelley DE, He J, Menshikova EV, and Ritov VB. Dysfunction of mitochondria in human skeletal muscle in Type 2 diabetes. Diabetes. 2002;51(10):2944-50. https://doi.org/10.2337/diabetes.51.10.2944 PMid:12351431 DOI: https://doi.org/10.2337/diabetes.51.10.2944

Liang H, Balas B, Tantiwong P, Dube J, Goodpaster BH, O’Doherty RM, et al. Whole body overexpression of PGC-1 α has opposite effects on hepatic and muscle insulin sensitivity. Am J Physiol Endocrinol Metab. 2009;296(4):E945-54. https://doi.org/10.1152/ajpendo.90292.2008 PMid:19208857 DOI: https://doi.org/10.1152/ajpendo.90292.2008

Lin J, Handshin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005;1(6):361-70. PMid:16054085 DOI: https://doi.org/10.1016/j.cmet.2005.05.004

Marinho R, Mekary RA, Muñoz VR, Gomes RJ, Pauli JR, de Moura LP. Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state. Diabetol Metab Syndr. 2015;7:67. https://doi.org/10.1186/s13098-015-0064-x PMid:26288661 DOI: https://doi.org/10.1186/s13098-015-0064-x

Huertas JR, Casuso RA, Agustín PH, Cogliati S. Stay fit, stay young: Mitochondria in movement: The role of exercise in the new mitochondrial paradigm. Oxid Med Cell Longev. 2019;2019:7058350. https://doi.org/10.1155/2019/7058350 PMid:31320983 DOI: https://doi.org/10.1155/2019/7058350

Haase TN, Ringholm S, Leick L, Biensø RS, Kiilerich K, Johansen S, et al. Role of PGC-1α in exercise and fasting-induced adaptations in mouse liver. Am J Physiol Regul Integr Comp Physiol. 2011;301(5):R1501-9. https://doi.org/10.1152/ajpregu.00775.2010 PMid:21832205 DOI: https://doi.org/10.1152/ajpregu.00775.2010

Liang H, Bai Y, Li Y, Richardson A, Ward WF. PGC-1α-induced mitochondrial alterations in 3T3 fibroblast cells. Ann N Y Acad Sci. 2007;1100(1):264-79. PMid:17460188 DOI: https://doi.org/10.1196/annals.1395.028

Machrina Y, Harun AL, 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.

Matiello R, Fukui RT, Silva ME, Rocha DM, Wajchenberg BL, Azhar S, et al. Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running. Nutr Metab (Lond). 2010;7(1):36. https://doi.org/10.1186/1743-7075-7-36 PMid:20433743 DOI: https://doi.org/10.1186/1743-7075-7-36