:: Volume 30, Issue 3 (8-2022) ::
Journal of Ilam University of Medical Sciences 2022, 30(3): 1-11 Back to browse issues page
Effect of a Six-week Endurance Exercise Program and Empagliflozin Consumption on Some Structural and Functional Indices of the Heart in Male Diabetic Rats
Eftekhar Mohammadi1 , Mohammad Fathi * 2, Farzaneh Chehel Cheraghi3 , Afshin Nazari4
1- Dept of General Courses & Basic Sciences, Faculty of Economics & Maritime Management, Khorramshahr University of Marine Science and Technology, Khorramshahr, Iran
2- Deptof Physical Education and Sports Sciences, Faculty of Literature and Humanities, Lorestan University, Khorramabad, Iran , fathi.m@lu.ac.ir
3- Dept of Anatomical Sciences, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
4- Dept of Physiology and Pharmacology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
Abstract:   (1154 Views)
Introduction: Type 2 diabetes is a major risk factor for cardiovascular diseases. Endurance training and empagliflozin were reported to have notable effects on heart structure and function. This study aimed to investigate the effect of six weeks of endurance training and empagliflozin intake on some structural and functional indicators of the heart in diabetic male rats.
Material & Methods: In this study, a total of 40 male Wistar rats (mean±SD weight: 253.09±12.92 g, aged: 8-10 weeks) were randomly divided into five equal groups, 1) healthy control, 2) diabetic control, 3) diabetic+empagliflozin, 4) diabetic+endurance training, and 5) diabetic+endurance training+empagliflozin and kept in laboratory conditions. Induction of diabetes was performed in rats after completion of the familiarization protocol for two weeks and after 12 h of food deprivation by intraperitoneal injection of streptozotocin  (STZ) solution at a dose of 50 mg /kg. The glucose level of 300 mg/dL was considered diabetic. The training groups practiced endurance training, five days per week for six weeks. The drug groups also received empagliflozin (10 mg/kg) daily by gavage. The animals were anesthetized 48 h after the end of the protocol and cardiac function was recorded using echocardiography. Subsequently, cardiac tissue was isolated and dissected. One-way analysis of variance (ANOVA) and Kruskal-Wallis tests were used for statistical analysis of data in SPSS software (version 27) and Graph Pad Prism software (version 9).
(Ethic code: LU.ECRA.2021.63)
Findings: The results showed significant differences between study groups in terms of left ventricular end-systolic thickness (P=0.011) and left ventricular end-systolic volume (P=0.008). The results of the post-hoc test showed that left ventricular end-systolic thickness in the diabetic control group was significantly higher, compared to the healthy control group (P=0.012). On the other hand, left ventricular end-systolic thickness in diabetes+exercise+empagliflozin was significantly lower, compared to the diabetic control group (P=0.020). Moreover, left ventricular end-systolic volume in the diabetic control group was significantly higher, compared to healthy controls (P=0.006), and left ventricular end-systolic volume in the diabetes+exercise+empagliflozin group was significantly lower than that in the diabetic control group (P=0.017). No significant differences were observed in other structural and functional indices of the heart (P≥0.05).
Discussion & Conclusion: The results of the present study showed that the combination of empagliflozin use and endurance training has a positive impact on the structure and function of the heart compared to the adoption of each (empagliflozin use and training) alone.
 
Keywords: Diabetes, Empagliflozin, Endurance training, Heart anatomy, Heart function
Full-Text [PDF 1205 kb]   (558 Downloads)    
Type of Study: Research | Subject: animal physiology
Received: 2021/10/27 | Accepted: 2022/01/3 | Published: 2022/08/6
References
1. Mohammadi E, Fathi M , ChehelCheraghi F , Nazari A. The effect of six weeks of endurance training and Empagliflozin intake on weight and electrical changes of the heart in male Wistar rat's diabetic with STZ. Yafte 2021; 23:199-210.
2. Cho N, Shaw J, Karuranga S, Huang Yd, da Rocha Fernandes J, Ohlrogge A, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271-81. doi: 10.1016/j.diabres.2018.02.023.
3. Zheng J, Cheng J, Zheng S, Zhang L, Guo X, Zhang J, et al. Physical exercise and its protective effects on diabetic cardiomyopathy: what is the evidence? Front Endocrinol (Lausanne) 2018;9:729. doi: 10.3389/fendo.2018.00729.
4. Banitalebi E, Ghahfarrokhi MM, Faramarzi M, Earnest C. Sprint interval training vs. combined aerobic+resistance training in overweight women with type 2 diabetes. J Sports Med Phys Fitness 2020; 61:712-24. doi: 10.23736/S0022-4707.20.11105-8.
5. Grubić Rotkvić P, Planinić Z, Liberati Pršo A-M, Šikić J, Galić E, Rotkvić L. The Mystery of Diabetic Cardiomyopathy: From Early Concepts and Underlying Mechanisms to Novel Therapeutic Possibilities. Int J Mol Sci 2021;22:5973. doi: 10.3390/ijms22115973
6. Banitalebi E, Ghahfarrokhi MM, Faramarzi M, Nasiri S. The effects of 10-week different exercise interventions on Framingham risk score and metabolic syndrome severity scores in overweight women with type 2 diabetes. J Shahrekord Uni Med Sci 2019;21:1-8. doi: 10.34172/jsums.2019.01
7. Rashidi Z, Beigi R, Ghahfarrokhi MM, Faramarzi M, Banitalebi E, Jafari T, et al. Effect of elastic band resistance training with green coffee extract supplementation on adiposity indices and TyG-related Indicators in Obese Women. Obesity Med 2021;24:100351. doi :10.1016/j.exger.2020.110884
8. Bell DS. Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes care 2003;26:2433-41. doi: 10.2337/diacare.26.8.2433.
9. Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000;101:2271-6. doi: 10.1161/01.cir.101.19.2271.
10. Shah AM, Hung C-L, Shin SH, Skali H, Verma A, Ghali JK, et al. Cardiac structure and function, remodeling, and clinical outcomes among patients with diabetes after myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. Am Heart J 2011;162:685-91. doi: 10.1016/j.ahj.2011.07.015.
11. Abdi-Ali A, Miller RJ, Southern D, Zhang M, Mikami Y, Knudtson M, et al. LV mass independently predicts mortality and need for future revascularization in patients undergoing diagnostic coronary angiography. JACC Cardiovasc Imaging 2018;11:423-33. doi: 10.1016/j.jcmg.2017.04.012.
12. Lee W-S, Kim J. Application of Animal Models in Diabetic Cardiomyopathy. Diabetes Metab J 2021;45:129-45. doi: 10.4093/dmj.2020.0285
13. Kuhre RE, Ghiasi SM, Adriaenssens AE, Albrechtsen NJW, Andersen DB, Aivazidis A, et al. No direct effect of SGLT2 activity on glucagon secretion. Diabetologia 2019;62:1011-23. doi : 10.1007/s00125-019-4849-6
14. Cahn A, Cernea S, Raz I. An update on DPP-4 inhibitors in the management of type 2 diabetes. Expert Opin Emerg Drugs 2016;21:409-19. doi: 10.1080/14728214.2016.1257608
15. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 26:373:2117-28. doi: 10.1056/NEJMoa1504720.
16. Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 2018;122 :624-38. doi: 10.1161/CIRCRESAHA.117.311586.
17. Zhou Y, Wu W. The sodium-glucose co-transporter 2 inhibitor, empagliflozin, protects against diabetic cardiomyopathy by inhibition of the endoplasmic reticulum stress pathway. Cell Physiol Biochem 2017;41:2503-12. doi: 10.1159/000475942.
18. Joshi SS, Singh T, Newby DE, Singh J. Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure. Heart 2021;107:1032-8. doi: 10.1136/heartjnl-2020-318060
19. Pham D, Rocha NDA, McGuire DK, Neeland IJ. Impact of empagliflozin in patients with diabetes and heart failure. Trends Cardiovasc Med 2017;27:144-51. doi: 10.1016/j.tcm.2016.07.008.
20. Verma S. Potential mechanisms of sodium-glucose co-transporter 2 inhibitor-related cardiovascular benefits. Am J Cardiol 2019;124:S36-S44. doi: 10.1016/j.amjcard.2019.10.028.
21. Fogante M, Agliata G, Basile MC, Compagnucci P, Volpato G, Falanga U, et al. Cardiac Imaging in Athlete’s Heart: The Role of the Radiologist. Medicina 2021;57:455. doi: 10.3390/medicina57050455
22. Chengji W, Xianjin F. Exercise protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway in rats. J Cell Physiol 2019;234:1682-8. doi: 10.1002/jcp.27038.
23. Gunadi JW, Tarawan VM, Setiawan I, Lesmana R, Wahyudianingsih R, Supratman U. Cardiac hypertrophy is stimulated by altered training intensity and correlates with autophagy modulation in male Wistar rats. BMC Sports Sci Med Rehabil 2019;11:1-9. doi: 10.1186/s13102-019-0121-0
24. Oláh A, Kovács A, Lux Á, Tokodi M, Braun S, Lakatos BK, et al. Characterization of the dynamic changes in left ventricular morphology and function induced by exercise training and detraining. Int J Cardiol 2019;277:178-85. doi: 10.1016/j.ijcard.2018.10.092
25. Verboven M, Cuypers A, Deluyker D, Lambrichts I, Eijnde BO, Hansen D, et al. High intensity training improves cardiac function in healthy rats. Sci Rep 2019;9:1-8. doi: 10.1038/s41598-019-42023-1
26. Mohammadi E, Nikseresht F. Effect of 8 Weeks of Incremental Endurance Training on the Activity of Superoxide Dismutase Enzyme and Malondialdehyde Levels of Cardiac Tissue of Rats with Type 2 Diabetes. ijdld 2020; 19:261-68
27. King AJ. The use of animal models in diabetes research. Br J Pharmacol 2012;166:877-94. doi: 10.1111/j.1476-5381.2012.01911.x.
28. Luippold G, Klein T, Mark M, Grempler R. Empagliflozin, a novel potent and selective SGLT‐2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin‐induced diabetic rats, a model of type 1 diabetes mellitus. Diabetes Obes Metab 2012;14:601-7. doi: 10.1111/j.1463-1326.2012.01569.x.
29. Mohammadi E, Nikseresht F. Effect of 8 Weeks of Incremental Endurance Training on Antioxidant Enzymes and Total Antioxidant Status of Cardiac Tissue in Experimental Diabetic Rats. JSSU 2020; 28 :2490-2501
30. Mihm MJ, Seifert JL, Coyle CM, Bauer JA. Diabetes related cardiomyopathy time dependent echocardiographic evaluation in an experimental rat model. Life Sci 2001;69:527-42. doi: 10.1016/s0024-3205(01)01141-9
31. Howarth F, Jacobson M, Shafiullah M, Adeghate E. Long‐term effects of streptozotocin‐induced diabetes on the electrocardiogram, physical activity and body temperature in rats. Exp Physiol 2005;90:827-35. doi: 10.1113/expphysiol.2005.031252
32. White Jr JR. Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence. Ann Pharmacother 2015;49:582-98. doi: 10.1177/1060028015573564.
33. Lee H-C, Shiou Y-L, Jhuo S-J, Chang C-Y, Liu P-L, Jhuang W-J, et al. The sodium–glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats. Cardiovasc Diabetol 2019;18:1-13. doi: 10.1186/s12933-019-0849-6.
34. Bolinder J, Ljunggren Ö, Johansson L, Wilding J, Langkilde A, Sjöström C, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 2014;16:159-69. doi: 10.1111/dom.12189.
35. Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-
36. the-art review. J Am Coll Cardiol 2020;75:422-34. doi: 10.1016/j.jacc.2019.11.031.
37. Searls YM, Smirnova IV, Fegley BR, Stehno-Bittel L. Exercise attenuates diabetes-induced ultrastructural changes in rat cardiac tissue. Med Sci Sports Exerc 2004;36:1863-70 doi: 10.1249/01.mss.0000145461.38224.ec.
38. Riyahi F, Riyahi S, Yaribeygi H. Diabetes and role of exercise on its control; A systematic. Health Res J 2016;1:113-21. doi:org/10.20286/hrj-010204
39. Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes care 2010;33:e147-e67. doi: 10.2337/dc10-9990
40. Chiang SL, Heitkemper MM, Hung YJ, Tzeng WC, Lee MS, Lin CH. Effects of a 12-week moderate-intensity exercise training on blood glucose response in patients with type 2 diabetes: A prospective longitudinal study. Medicine 2019;98. doi: 10.1097/MD.0000000000016860
41. Nery C, De Moraes SRA, Novaes KA, Bezerra MA, Silveira PVDC, 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;21:400-15. doi: 10.1016/j.bjpt.2017.06.004
42. Forero R, Nahidi S, De Costa J, Mohsin M, Fitzgerald G, Gibson N, et al. Application of four-dimension criteria to assess rigour of qualitative research in emergency medicine. BMC Health Serv Res 2018;18:1-11. doi: 10.1186/s12913-018-2915-2
43. Wang H, Bei Y, Lu Y, Sun W, Liu Q, Wang Y, et al. Exercise prevents cardiac injury and improves mitochondrial biogenesis in advanced diabetic cardiomyopathy with PGC-1α and Akt activation. Cell Physiol Biochem 2015;35:2159-68. doi: 10.1159/000374021.
44. Yurista SR, Silljé HH, Oberdorf‐Maass SU, Schouten EM, Pavez Giani MG, Hillebrands JL, et al. Sodium–glucose co‐transporter 2 inhibition with empagliflozin improves cardiac function in non‐diabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail 2019;21:862-73. doi: 10.1002/ejhf.1473.

Ethics code: LU.ECRA.2021.63



XML   Persian Abstract   Print



Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 30, Issue 3 (8-2022) Back to browse issues page