تاثیر تمرین تناوبی و عسل آویشن بر مسیر miR-423-5p، FAM3A، AKt2 کبدی موش‌های صحرایی دیابتی نوع دو

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دبیر آموزش و پرورش ناحیه یک شیراز

2 هیات علمی دانشگاه آزاد اسلامی واحد تهران جنوب، دانشکده تربیت بدنی و علوم ورزشی، گروه فیزیولوژی ورزش، دانشیار

3 هیات علمی دانشگاه آزاد اسلامی واحد تهران جنوب، دانشکده تربیت بدنی و علوم ورزشی، گروه فیزیولوژی ورزشی، استادیار

4 گروه تربیت بدنی و علوم ورزشی، دانشگاه ازاد اسلامی واحد علوم تحقیقات تهران، تهران، ایران.

چکیده

مقدمه: میکروRNAها در ایجاد دیابت نوع۲ و بروز عوارض آن دخالت دارند. هدف پژوهش حاضر مطالعه تاثیر تمرین تناوبی و عسل آویشن بر چگونگی بیان ژن های مسیر miR-423-5P- FAM3A-AKt2 در بافت کبدی موش‌های صحرایی دیابتی نوع۲ بود.
روش‌ کار: ۳۶ سرموش نرویستار پس از۲۰هفته تغذیه با رژیم غذایی پرچرب و سپس تزریق استرپتوزتوسین به میزان ۲۵میلی‌گرم/کیلوگرم برای القا دیابت نوع۲، به چهارگروه دیابتی با کبد چرب: کنترل، تمرین تناوبی، عسل آویشن و تمرین همراه با عسل تقسیم شدند. هشت هفته تمرین تناوبی، پنج جلسه در هفته برای گروه های تمرینی انجام و عسل آویشن روزانه با دُز ۳ گرم/کیلوگرم به روش گاواژ به موش‌های گروه مداخله تغذیه ای خورانده شد. میزان بیان ژن هایmiR-423-5P، mRNA FAM3Aو mRNA AKt2 کبد با استفاده از روش RT-PCR و بکارگیری کیت های مخصوص اندازه گیری و یافته ها با استفاده از آزمون تحلیل واریانس دو عاملی و آزمون تعقیبی بونفرونی مورد تجزیه و تحلیل قرار گرفت.
نتایج: در گروه های تجربی نسبت به گروه کنترل بیان ژن miR-423-5P کاهش معنی دار و بیان mRNA FAM3A افزایش غیرمعنی دار داشت و بیان mRNA AKt2 در گروه های تمرین و تمرین همراه با عسل نسبت به گروه کنترل افزایش معنی دار و در گروه عسل نیز افزایش داشت که از نظر آماری معنی دار نبود.( 0/05>P)
نتیجه‌گیری: به نظر می‌رسد تمرین تناوبی و مصرف عسل آویشن هر دو به تنهایی وبه صورت تعاملی با تاثیر بیشتر، بتوانند به ایجاد تغییرات مطلوب در بیان ژن های مذکور در کبد موش‌های صحرایی دیابتی نوع ۲ کمک کنند.

کلیدواژه‌ها


عنوان مقاله [English]

Effect of High Intensity Interval Training and Thyme Honey on Hepatic miR-423-5P, FAM3A, Akt2 Pathway of Type ll Diabetic rats

نویسندگان [English]

  • marjan abdi ardekani 1
  • Abdol Ali Banaei Far 2
  • Sajjad Arshadi 3
  • Hossein Abednatanzi 4
1 Teacher of district one of education in Shiraz
2 Department of Sports Physiology, Faculty of Physical Education and Sport Sciences, Islamic Azad University, South Tehran Branch, Tehran. Iran.
3 Department of Sports Physiology, Faculty of Physical Education and Sport Sciences, Islamic Azad University, South Tehran Branch, Tehran. Iran.
4 Department of Physical Education and Sport Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
چکیده [English]

Introduction: Micro-RNAs are effective in inflicting diabetes type II and its side effects. The Purpose of this study was to evaluate the effect of High Intensity Interval Training & thyme honey on expression of the genes of the hepatic miR-423-5P - FAM3A-AKt2 pathway in rats.
Materials and Methods: 36 male rats were fed with high-fat diets for 20weeks and were then injected streptozotocin (25 mg/kg) in order to inflict diabetes type II. The 36rats were then divided into four groups: Control, regular exercise group, nutritional intervention group and exercise with nutritional intervention group. Regular exercise included five sessions a week for eight weeks and nutritional intervention was done at a dosage of 3 g/kg of thyme honey using a gauge method. The amount of expression of miR-423-5P, mRNA FAM3A and mRNA AKt2 genes of the liver were assessed using RT-PCR and evaluation kits. The obtained findings were analyzed using the two-way analysis of variance and Bonferroni post hoc test.
Results: Expression of the miR-423-5P gene was significantly lower in all groups compared to control, expression of mRNA FAM3 had insignificant increase and expression of mRNA AKt2 had a significant increase in groups of regular exercise and exercise with nutritional intervention. This gene had an insignificant increase of expression in the group with only nutritional intervention. (p value<0.05)
Discussion: It seems that HIIT & consumption of thyme honey, both alone and interactively with greater effectiveness, can change in expression of the mentioned gene in liver of rats with diabetes type II.

کلیدواژه‌ها [English]

  • Diabetes Type II
  • miR-423-5P - FAM3A -AKt2
  • HIIT
  • Thyme Honey
  1. Sapra A, Bhandari P. Diabetes Mellitust. In: Eberhardt M, Blepharitis RG, Editors. StatPearls. Treasure Island (FL). Massachusetts: StatsPearls Publishing. (2020).
  2. Adulcikas J, Sonda S, Norouzi Sh, Sohal S S, Myers S. Targeting the Zinc Transporter ZIP7 in the Treatment of Insulin Resistance and Type 2 Diabetes. Nutrients. (2019). Feb 15;11(2):408. doi: 10.3390/nu11020408.
  3. Pescatello LS, Riebe D, Thompson PD. ACSM’s guidelines for exercise testing and prescription. Philadelphia: Lippincott Williams & Wilkins. (2014)
  4. Miller 2015. Physiology and physiopathology of gastrointestinal tract and liver Nutrition and anesthesia considerations in liver surgery.translated by bb Mona Razavi, Tehran. Artin Teb. (2016). V19.p:57-59.
  5. H.khanegie K .Comparison of the effects of nettle and white nettle on the expression of genesLiver and kidney cyclooxygenase-2 and caspase-3 in streptozotocin-induced diabetic rats. Research project. East Gilan Paramedical School (Medical Biotechnology Research Center).(2014). (In Persian)
  6. Wackerhage H. Molecular Exercise Physiology An Introduction to, translated by Farhad Darianush, .Tehran, Hatami Publications.(2016).p:278
  7. Kramer W J, Flek, S J. Desgenes, M R. Exercise physiology integrating theory and application translated by Farhad Darianush and Abbas Ali Gaini, Tehran, Etmanat Publications.(2015).p:424 (Date of publication of the work in the origninal language, 2012).
  8. Tidos P M, Russell Topling E, Houston, M E. Biochemistry primer for exercise sciences. translated by Abbas Ali Gaini and Ali Samadi Tehran, Hatami Publications.(2015).p:368
  9. Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. Diabetes mellitus, a microRNA-related disease. Translational research : the journal of laboratory and clinical medicine. (2011).  157(4), 253-64.
  10. Ferland-McCollough D, Ozanne S E, Siddle K, Willis A E, Bushell M. (2010). The involvement of microRNAs in Type 2 diabetes. Biochemical Society transactions. (2010).  38(6), 1565-70.
  11. Joglekar M V, Parekh V S, Hardikar A A. Islet-specific microRNAs in pancreas development, regeneration and diabetes. Indian journal of experimental biology. (2011).  49(6), 401-8.
  12. Vatandoost N, Momenzadeh S, Kamali S, Salehi R. Evaluation of relative expression of miR103 in peripheral blood mononuclear cells of rats with type 2 diabetes and pre-diabetes. Isfahan Medical School Journal,(2014). 32, 306, 1756-174
  13. Osmai M, Osmai Y, Bang-Berthelsen C H, Pallesen E M, Vestergaard A L, Novotny G W, Mandrup-Poulsen T. MicroRNAs as regulators of beta-cell function and dysfunction. Diabetes/metabolism research and reviews. (2016). 32(4), 334-49.
  14. Agarwal P, Srivastava R, Srivastava A K, Ali S, Datta, M. miR-135a targets IRS2 and regulates insulin signaling and glucose uptake in the diabetic gastrocnemius skeletal muscle. Biochimica et biophysica acta. (2013). 1832(8), 1294-303.
  15. Elton T S, Selemon H, Elton S M, Parinandi N L. Regulation of the MIR155 host gene in physiological and pathological processes. Gene. (2013).  532(1), 1-12.
  16. Huang Y, Yan Y, Xv W, Qian G, Li C, Zou H, Li Y. A New Insight into the Roles of MiRNAs in Metabolic Syndrome. BioMed research international. (2018).2018, 7372636.
  17. Chien H Y, Lee T P, Chen C Y, Chiu Y H, Lin Y C, Lee L S, Li W C. Circulating microRNA as a diagnostic marker in populations with type 2 diabetes mellitus and diabetic complications. Journal of the Chinese Medical Association : JCMA. (2015).78(4), 204-11.
  18. Aghaiee Bakhtiari H, Arefian E, Hosseine Rad M A & et al. MiRNAs and their role in biological and pathological pathways. Electronic version of the Stem Cell Research and Technology Center. Date of creation: November (2017).P:251&26. www.bonbiotech.ir
  19. Wang C, Wan S, Yang T, Niu D, Zhang A, Yang C, Wang J. Increased serum microRNAs are closely associated with the presence of microvascular complications in type 2 diabetes mellitus. Scientific reports. (2016). 6, 20032.
  20. Yang W, Wang J, Chen Z, Chen J, Meng Y, Chen L, Yang, J. NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway. Diabetes. (2017). 66(7), 1819-32.
  21. Zhang Y, Wan J, Liu S, Hua T, Sun Q. Exercise induced improvements in insulin sensitivity are concurrent with reduced NFE2/miR-432-5p and increased FAM3A. Life sciences, (2018). 207, 23-9.
  22. Xu W,  Liang M ,  Zhang Y , Huang K ,  Wang Endothelial FAM3A positively regulates post-ischaemic angiogenesis, EBioMedicineMay .( 2019 ) 43:32-42.
  23. Chen Z, Liu X, Luo Y, Wang J, Meng Y, Sun L, Yang, J. Repurposing Doxepin to Ameliorate Steatosis and Hyperglycemia by Activating FAM3A Signaling Pathway. Diabetes. (2020). 69(6), 1126-39.
  24. Kang T, Peng D, Bu G, Gu H, Zhang F, Zhang R.Transcriptional regulation analysis of FAM3A gene and its effect on adipocyte differentiation.Gene.(2019). Dec 20; 595(1):92-98.
  25. Yang W, Chi Y, Meng Y, Chen Z, Xiang R, Yan H, Yang J. FAM3A plays crucial roles in controlling PDX1 and insulin expressions in pancreatic beta cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. (2020). 34(3), 3915-31.
  26. Chen Z, Wang J, Yang W, Chen J, Meng Y, Geng B, Cui Q, Yang J. FAMA mediates PPARS protection in liver ischemia- reperfusion injury by activating AKt survival pathway and repressing inflammation and oxidative stress.Oncotarget.(2017).Jul 25;8(30):49882-49896.
  27. Kandel E S, Hay N. The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Experimental cell research. (1999).  253(1), 210-29.
  28. Qarekhanlu R, Molanouri Shamsi M .A Look at Cellular and Molecular Adaptations to Exercise. First Edition, Tehran, Hatami Publications.(2015).p:128
  29. Roberts CK, Barnard RJ. Effects of exercise of Applied Physiology. 2005; 98 (1): 3-30.
  30. Timmons JA, Baar K, Davidson PK, Atherton PJ. IS irisin a human exercise gene? Nature. 2012; 488 (7413): E9-10.
  31. Wackerhage H. Molecular exercise physiology: and introduction. London: Routledge; 2014.
  32. Akshintala D, Chugh R, Amer F, Cusi K &et al. Nonalcoholic Fatty Liver Disease: The Overlooked Complication of Type 2 Diabetes.2019. In: Endotext [Internet]. South Dartmouth : NBK544043. Free Books & Documents.
  33. Borhade BM. Singh SH. Diabetes Mellitus And Exercise. 2020.In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. Free Books & Documents
  34. Erejuwa OO. Effect of honey in diabetes mellitus: matters arising J Diabetes Metab Disord.2014. Jan 29;13(1):23. doi: 10.1186/2251-6581-13-23
  35. Alvarez-Suarez JK, Tulpani S, Romandini S, Bertoli E, Battino M. human health: a review. Mediterranean Journal of Nutrition and Metabolism. 2010; 3(1): 15-23.
  36. Ajibola A. Novel Insights into the Health Importance of Natural Honey. Malays J Med Sci.2015. Sep;22(5):7-22
  37. Bobiş O, D Dezmirean DS, Moise AR. Honey and Diabetes: The Importance of Natural Simple Sugars in Diet for Preventing and Treating Different Type of Diabetes. Oxid Med Cell Longev.2018. Feb 4:4757893. doi: 10.1155/2018/4757893
  38. Al Aamri ZM, Ali BH. Does honey have any salutary effect against streptozotocin - induced diabetes in rats? J Diabetes Metab Disord.2017. Jan 24;16:4. doi: 10.1186/s40200-016-0278
  39. Vallinou NG.Gounari P.Skourtis A.Panagos J.Kazazis CH.Honey and its anti-inflammatory. Anti-bacterial and anti-oxidant properties.General Medicine.2014.2:2
  40. Korkmaz A, Kolankaya D. Anzer honey prevents N-ethylmaleimide-induced liver damage in rats. Exp Toxicol Pathol.2009. Jul;61(4):333-7. doi: 10.1016/j.etp.2008.07.005
  41. Xiao J, Liu Y, Xing F, Leung TM, Liong C, Tipoe GL. Bee's honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein-NLRP3 inflammasome E urJ Nutr.2016. Jun;55(4):1465-77 doi: 10.1007/s00394-015-0964-4
  42. Erejuwa OO, Gurtu S, Sulaiman SA, Wahab MS, Sirajudeen KN, Salzihan MD .Salleh MD. Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats. nt J Vitam Nutr Res.2010. Jan;80(1):74-82. doi: 10.1024/0300
  43. Ramli NZ, Chin KY, Zarkasi KA, Ahmad F. A Review on the Protective Effects of Honey against Metabolic Syndrome. Nutrients.2018. Aug 2;10(8):1009. doi: 10.3390/nu10081009
  44. Nasrolahi O, Heidari R, Rahmani F, Farokhi F. Effect of natural honey from Ilam and metformin for improving glycemic control in sterptozotocin induced diabetic rats. Avicenna J Phytomed.2012. Fall 2012;2(4):212-21
  45. Erejuwa OO, Sulaiman SA, Ab Wahab MS. Honey: a novel antioxidant. Molecules.2012. Apr 12;17(4):4400-23. doi: 10.3390/molecules17044400
  46. Cianciosi D, Forbes-Hernández TY, Afrin S, Gasparrini M, Reboredo-Rodriguez P& et al. Phenolic Compounds in Honey and Their Associated Health Benefits: A Review. Molecules.2018.Sep11;23(9):2322.doi:10.3390/molecules23092322
  47. Bahrami M, Jafari AA, Hosseini S, ForuzanfarMH,& et al. Effects of natural honey consumption in diabetic patients: an 8-week randomized clinical trial. Int J Food Sci Nutr.2009. Nov;60(7):618-26
  48. Nemoseck TM, Carmody EG, Evanson AF, Gleason M& et al. Honey promotes lower weight gain, adiposity, and triglycerides than sucrose in rats. Nutr Res.2011. Jan;31(1):55-60. doi: 10.1016/j.nutres.2010.11.002
  49. Selavaziyan A.Abdolahpour F.Esmaeili A.Sepahvand F.Azadpour MAntioxidant activity and antimicrobial properties of two types of honey due to changes in the diet of bees in comparison with other honeys produced in Abestan region of Khorramabad city. Journal of Lorestan University of Medical Sciences.2015. Vo 17. No 3. Series 65. .(In Persian)
  50. Preedy VR.Essential oils in food preservation, flavor and safty.Science Direct book.2016.Chapter 94- Thyme oils.pp.825-834
  51. Farnam S. The effect of thyme species on animal and poultry nutrition, The Third National Conference on Environmental and Agricultural Research in Iran.2015. Tehran. August22
  52. Shishebor F.Tehrani M.Jalali MT.Latifee SM. Comparison of blood sugar index of two types of Iranian honey with different fructose to glucose ratio. Iranian Journal of Endocrinology and Metabolism.2012. Vol. 14. No. 5. pp: 479-483.(In Persian).
  53. Meo SA, Ansari MJ, Sattar K, Chaudhary HU, Hajjar W, Alasiri S. Honey and diabetes mellitus: Obstacles and challenges - Road to be repaired. Saudi J Biol Sci.2017. Jul;24(5):1030-1033. doi: 10.1016/j.sjbs.2016.12.020. Epub 2017 Jan 11
  54. 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 Aug 8; 79(11): 1100–1107
  55. 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 52 (2005) 313–320
  56. A, Fattahi Bafghi. A, The effect of high intensity interval training and corcomin supplement on plasma glucose concentration and insulin resistance in diabetic rats. Shahid Sadoughi Journal of Medical Sciences, Yazd. Volume 25, Number 12, March 2017. [In Persian)
  57. Thomas C, Bishop D, Moore-Morris T, Mercier J. Effects of high intensity training on MCT1, MCT4, and NBC expressions in rat skeletal muscles: influence of chronic metabolic alkalosis. American Journal of Physiology- Endocrinology and Metabolism.2007; 293(4):E916-E22
  58. Erejuwa OO, Nwobodo NN, Akpan JL, Okorie YA.& et all. Nigerian Honey Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Rats. Nutrients 2016, 8, 95; doi: 10.3390/nu8030095
  59. Mehran M, Safaei A, Taghizadeh M, Hatami A, Hosseini. H, A study of the essential oils of seven types of thyme and a comparison of their antioxidant properties. Journal of Medicinal Plants. 15(2), 58(2).page 134-140.2016. (In Persian)
  60. Rodrigues B, Figueroa DM, Mostarda CT, Heeren MV, Irigoyen MC, De Amgelis K. Maximal exercise test is useful method for physical capacity and oxygen consumption determination in streptozotocin-diabetic rats. Cardiocascular Diabetology. 2007; 6(1): 38.
  61. Ortega F J, Mercader J M, Catalán V, Moreno-Navarrete J M, Pueyo N, Sabater M, Fernández-Real J M. Targeting the circulating microRNA signature of obesity. Clinical chemistry. (2013).  59(5), 781-92.
  62. Gjorgjieva M, Sobolewski C, Dolicka D, Correia de Sousa M, Foti  miRNAs and NAFLD: from pathophysiology to therapy. Gut. (2019). 68(11), 2065-79.
  63. Liu CH, Ampuero J, Gil-Gómez A, Montero-Vallejo R, Rojas Á, Muñoz-Hernández R, Romero-Gómez M. miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis. Journal of hepatology. (2018).69(6), 1335-1348.
  64. Wang C, Chen Z, Li S, Zhang Y, Jia S, Li J, Yang J. Hepatic overexpression of ATP synthase β subunit activates PI3K/Akt pathway to ameliorate hyperglycemia of diabetic mice. Diabetes. (2014). 63(3), 947-59.
  65. Risso G, Blaustein M, Pozzi B, Mammi P, Srebrow A. Akt/PKB: one kinase, many modifications. The Biochemical journal. (2015). 468(2), 203-14.
  66. Qi J, Yang B, Ren C, Fu J, Zhang J. Swimming Exercise Alleviated Insulin Resistance by Regulating Tripartite Motif Family Protein 72 Expression and AKT Signal Pathway in Sprague-Dawley Rats Fed with High-Fat Diet. Journal of diabetes research. (2016), 1564386.
  67. Oliveira-Carvalho V, da Silva M M, Guimarães G V, Bacal F, & Bocchi E A. MicroRNAs: new players in heart failure. Molecular biology reports. (2013). 40(3), 2663-70.
  68. Li F, Bai M, Xu J, Zhu L, Liu C, Duan R. Long-Term Exercise Alters the Profiles of Circulating Micro-RNAs in the Plasma of Young Women. Frontiers in physiology. (2020).  11, 372.
  69. Taheri Gandmani M, Faramarzi M, Bani Talebi I, Hemmati, R. Evaluation of eight weeks of intermittent and continuous endurance training on MicroRNAs associated with reverse cholesterol transfer in elderly Wistar rats. Sports Physiology ,(2018).Fall, 39, 185 – 201.
  70. Párrizas M, Brugnara L, Esteban Y, González-Franquesa A, Canivell S, Murillo S, Novials ACirculating miR-192 and miR-193b are markers of prediabetes and are modulated by an exercise intervention. The Journal of clinical endocrinology and metabolism. (2015). 100(3), E407-15.
  71. Liu S X,   Zheng F ,  Xie K L  ,  Xie M R  ,  Jiang L J ,  Cai  Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis, Mol Ther Nucleic Acids, .(2019) . Dec 6;18:34-44.