Document Type : Research Paper
Authors
1 Ph.D. Student of Exercise physiology, Science and research branch, Islamic Azad University, Faculty of Humanities, Department physical education and sport science, Tehran, Iran.
2 Assistant Professor of Exercise Physiology, Science and research branch, Islamic Azad University, Faculty of Humanities, Department physical education and sport science, Tehran, Iran
3 Assistant Professor of Exercise Physiology, Sport Sciences Research Institute, Sport Medicine Research Center, Tehran, Iran
4 Associate Professor of Exercise Physiology, Science and research branch, Islamic Azad University, Faculty of Humanities, Department physical education and sport science, Tehran, Iran
Abstract
Type 2 diabetes is the most common endocrine disease that occurs due to glucose intolerance due to imbalance between reserves and insulin demand. Diabetes can also cause damage and cell death or apoptosis. The purpose of this study was to study the gene expression changes in apoptotic and anti-apoptotic indices in liver tissue and insulin resistance index after HIIT and Zataria multiflora extract in obese type 2 diabetic rats. The statistical population consisted of male Wistar rats weighing 110 ± 20 g, with 4-week-old male selected from Royan Institute. Wistar rats with the aim of familiarizing themselves with the environment for two weeks, were kept at about 190 ± 20 gr. All rats were fed a high-fat diet (45 to 60% fat) for 5 months or 20 weeks. After the rats became obese and reached an average weight of about 407 ± 50 g, to create a type 2 diabetic model, 25 mg STZ at a low dose per kg body weight was injected intraperitoneally as fasting glucose between 150 to 400 mg/dl was considered as a criterion for diabetes. All rats were diabetic and were divided into 4 groups (control, HIIT, Thyme, HIIT-Thyme). Rats with fasting glucose between 150 and 400 mg / dL were considered to have type 2 diabetes. HIIT protocol and gavage performed for eight weeks, five sessions per week with 2-minute alternation of 2 and 8 intervals with 80 to 90% vo2max and a one-minute rest cycle with 50 to 56% vo2max. Thyme extract was given by gavage at a dose of 200 mg / kg 5 days a week for eight week. Insulin resistance index was calculated using the formula and the expression of liver tissue apoptotic genes was also measured by RT-PCR. Statistical analysis was performed with one-way ANOVA and two-factor analysis of variance test for comparison between groups and determination of the effect size and post-hoc method. A significant level of p ≤ 0.05 was considered. Compared to the control group, HIIT led to a significant reduction in glucose and insulin resistance index (P<0.05). Periodic exercise and thyme extract also decreased Bax gene expression and increased Bcl2 expression in hepatocytes compared with controls (P<0.05). The results showed that HIIT with thyme extract in diabetic rats led to improved glycemic profile and changes in glucose and insulin levels, as well as positive and appropriate changes in the expression of hepatic and anti-apoptotic genes.
Keywords
- Shokrolahi Ardakani A, Abednatanzi H, Gholami M, Shakeri N. The effect of resistance training on g6pase gene expression in liver hepatocytes, glucose and insulin resistance levels in type 2 diabetic rats. Iranian Journal of Diabetes and Obesity. 12(14): URL: http://ijdo.ssu.ac.ir/article-1-544-en.html.(in Persian).
- Chahardoli M, Mahmoodi M, Hajizadeh M, Khoramdel Azad H, Khoshdel A, Mirzaei M. effect of aloe vera hydroalcoholic extract on blood glucose, serum insulin and the key enzymes in metabolic pathways of glycolysis and gluconeogenesis in hepatocytes of type 1 diabetic rats. Journal of Rafsanjan University of Medical Sciences. 2015;13(8):669-82. (in Persian).
- Jabbari E, Gholami M, Nikbakht H, Shakeri N, ghazaliyan F. Effect of aerobic training and L-carnitine supplementation on some apoptotic factors in diabetic rat liver. Razi Journal of Medical Sciences. 2019;26(7):131-40.
- Doustar Y, Mohajeri D, Rezaei A. Effects of grape seed extract on heart cells apoptosis in streptozotocin induced diabetic rats. Med Sci J Islam Azad Uni. 2012;21(3):168-74.
- Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A. Myocardial cell death in human diabetes. Circ Res; 2000;87:1123-32.
- Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroen. Hepatol; 2000;15:718–24.
- Mirdar Harijani Sh, Musavi N, Hamidian Gh. Effect of endurance swimming training during pregnancy on histology and apoptotic index of rats’ liver. Iranian South Medical Journal; 2015;18(1):54-63.
- Godin G, Desharnais R, Valois P, Lepage L, Jobin J, Bradet R. Differences in perceived barriers to exercise between high and low intenders: observations among different populations. American Journal Health Promotion. 1994;(8)4:279-85.
- Khajehlandi A, Abed Natanzi H, Nikbakht H. The effect of swimming training and aloe vera extract on lipid profile of male diabetic rats. Journal of Isfahan Medical School. 2017;34(411):1515-21. (In Persian).
- Shapiro K, Gong WC. Natural products used for diabetes. J Am Pharmacol Assoc. 2002;42:217-26.
- Naghdi Badi H, Makkizadeh M. Review of common thyme. J Med Plants. 2003;2(7):1-12.
- Rana P, Soni G. Antioxidant potential of thyme extract: alleviation of N-nitrosodie thylamine-induced oxidative stress. Hum Experiment Toxicol. 2008;27:215-21.
- Letchamo W, Xu HL, Gosselin A. Variations in photo synthesis and essential oil in thyme. J Plant physiol. 1995;147:29-37.
- Baynes LW, Thorpe SR. Role of oxidative stress in diabetic complication: a new perspective on an old paradigm. Diabetes. 1999;48:1-9.
- Zou Y, Li J, Lu C, Wang J, Ge J, Huang Y, et al. High-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Life Sci. 2006;79(11):1100–7.
- Zou F, Mao XQ, Wang N, Liu J, Ou-Yang JP. Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of ampk. Acta Pharmacol Sin. 2009;30:1607-15.
- Gheibi S, Bakhtiari Zadeh F, Ghasemi A. A review of the high-fat diet model - Streptozotocin for type 2 diabetes in rats. Journal of Endocrinology and Metabolism of Iran. 2016;18(2):135-48. (In Persian).
- K, Viswanad. B, Lydia Asrat, C.L. Kaul, P. Ramarao. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacological Research. 2005;52:313–20.
- Moeini Fard M, Hedayati M. Aluxan and streptozotocin, diabetes research tool. Journal of Applied Sports Physiology. 2014;10(20):13-22. (In Persian).
- Mehran M, Hoseini H, Hatami A, Taghizade M, Safaie A. Investigation of components of seven species of thyme essential oils and comparison of their antioxidant properties. J Med Plants. 2016;15(58):134-40.
- Yaghmaie P, Heydarian E, Poorbahman N. The regenerative effects of Thymus vulgaris extract on beta cells of pancreas of streptozotocin induced diabetic Wistar rats. Medical Sciences. 2011;21(3):162-67.
- Rodrigues B, Figueroa DM, Mostarda CT, Heeren MV, Irigoyen MC, De Angelis K. Maximal exercise test is a useful method for physical capacity and oxygen consumption determination in streptozotocin-diabetic rats. Cardiovasc Diabetol. 2007;6:38. Published 2007 Dec 13. doi:10.1186/1475-2840-6-38
- Akbarzadeh A, Fattahi bafghi A. The effect of high intencity interval training combined with curcumin supplementation on Plasma glucose concentration and insulin resistance in diabetic rats. JSSU. 2018;25(12):961-9. (In Persian).
- Rezaei R, Norshahi M, Bigdeli MR, Khodagholi F, Haghparast A. Effect of eight weeks of continuous and interval intense aerobic exercise on VEGFR-2 and VEGF-A values in the brain tissue of wistar rats. Journal of Exercise Physiology and Physical Activity. 2015;8(2):1213-21. (In Persian).
- Shidfar F, Jazayeri S, Mousavi SN, Malek M, Hosseini AF, Khoshpey B. Does Supplementation with Royal Jelly Improve Oxidative Stress and Insulin Resistance in Type 2 Diabetic Patients? Iran J Public Health. 2015;44(6):797-803.
- Jafari A, Pourrazi H, Nikookheslat S, Baradaran B. Effect of exercise training on Bcl-2 and Bax gene expression in the rat heart. Gene Cell Tissue. 2015;2(4):e32833.
- Ahmadiasl N, Ghadiri Soufi F, Alipour M, Bonyadi M, Sheikhzadeh F, Vatankhah A, Salehi I, Mesgari M. Effects of age increment and 36-week exercise training on antioxidant enzymes and apoptosis in rat heart tissue. Jour Sports Sci Med. 2007;6:243-249.
- Marsh SA, Laursen PB, Pat BK, Gobe GC, Coombes JS. Bcl-2 in endothelial cells is increased by vitamin E and α-lipoic acid supplementation but not exercise training. J Mole Cell Cardiol. 2005;38(3):445-51.
- Childs AC, Phaneuf SL, Dirks AJ, Phillips T, Leeuwenburgh C. Doxorubicin treatment in vivo cause’s cytochrome c release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2: Bax ratio. Can Res. 2002;62:4592-98.
- Mooren FC, Blöming D, Lechtermann A, Lerch MM,Völker K. Lymphocyte apoptosis after exhaustive and moderate exercise. Jour Appl Physiol. 2002;93(1):147-53.
- Skommer J, Wlodkowic D, Deptala A. Larger than life: mitochondria and the Bcl-2 family. Leuk Res. 2007;31:277-86.
- Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495-516.
- Maulik N, Sasaki H, Addya S, Das DK. Regulation of cardiomyocyte apoptosis by redoxsensitive transcription factors. FEBS Lett. 2000;485:7-12.
- Chen KC, Peng CC, Hsieh CL, Peng RY. Exercise ameliorates renal cell apoptosis in chronic kidney disease by intervening in the intrinsic and the extrinsic apoptotic pathways in a rat model. Evid Based Complem Altern Med. 2013;1-13.
- Kwak HB, Song W, Lawler JM. Exercise training attenuates age-induced elevation in Bax/Bcl2 ratio, apoptosis, and remodeling in the rat heart. FASEB J. 2006;20(6):791-3.
- Marin-Garcia J, Goldenthal MJ. Mitochondrial centrality in heart failure. Heart Fail Rev. 2008;13:137–50.
- French JP, Hamilton KL, Quindry JC, Lee Y, Upchurch PA, Powers SK. Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASB J. 2008;22:2862–71.
- 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-R115.
- Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 2001;413(6852):131.
- Rui L. Energy metabolism in the liver. Compr Physiol. 2014;4(1):177-197. doi:10.1002/cphy.c130024.
- Aoi W, Ichiishi E, Sakamoto N, Tsujimoto A, Tokuda H, Yoshikawa T. Effect of exercise on hepatic gene expression in rats: a microarray analysis. Life Sci. 2004;75(26):3117-28.
- Sharabi K, Lin H, Tavares CD, Dominy JE, Camporez JP, Perry RJ, et al. Selective chemical inhibition of PGC-1α gluconeogenic activity ameliorates type 2 diabetes. Cell. 2017;169(1):148-60.
- Way KL, Hackett DA, Baker MK, Johnson NA. The effect of regular exercise on insulin sensitivity in type 2 diabetes mellitus: a systematic review and meta-analysis. J Diabetes Metab. 2016;40(4):253-71.
- Lee S, Umano K, Shibamoto T, Lee S. Identification of volatile components in basil (ocimum basilicum L.) and thyme leaves (thymus vulgaris L.) and their antioxidant properties. Food Chemistry. 2005;91(1):131-7.
- Dorman HJD, Peltoketo A, Hiltunen R, Tikkanen MJ. Characterisation of the antioxidant properties of de-odourised aqueous extracts from selected Lamiaceae herbs. Food Chemistry. 2003;83(2):255-62.
- Testa R, Bonfigli AR, Genovese S, De Nigris V, Ceriello A. The possible role of flavonoids in the prevention of diabetic complications. Nutrients. 2016;8(5):310.
- Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas. Pharmacological Research. 2005;51(2):117-23.
- Yeylaghi Ashrafi MR, Abednatanzi H, Ghazalian F. The effect of eight weeks of high intensity interval training and n-chromosomal royal jelly on G6Pase gene expression in hepatocytes, glucose levels and insulin resistance in type 2 diabetic rats. Razi Journal of Medical Sciences. 2020(10) :135-150.URL: http://rjms.iums.ac.ir/article-1-6387-en.html (In Persian).
- Eizadi M, Soory R, Ravasi A, Baesy K, Choobineh S. Relationship between TCF7L2 relative expression in pancreas tissue with changes in insulin by high intensity interval training (HIIT) in type 2 diabetes Rats. Journal of Shahid Sadoughi University of Medical Sciences. 2017;24(12):981-93.
- Rashidi M, Soori R, Choobineh S, Ravasi AA, Baesi K. The effect of an aerobic exercise on MTNR1B gene expression, insulin and glucose levels in pancreas of induced diabetic rat with streptozotocin-nicotinamide. Journal of Knowledge & Health 2016;11(3):40-48.
- Alizadeh Pahavani H, Rajabi H, Nabiuni M, Motamedi P, Khaledi, N, Tayanloo A. The effect of aerobic exercise with medium and high intensity on the gene expression of bax (BCL2 associated X) and Bcl-2 (B-Cell Lymphoma 2) markers in rat myocard after ischemic-reperfusion.Sport Physiology. 2020;12(45):31-44. Doi: 10.22089/SPJ.2018.4598.1618 (In Persian).