14May 2020

STUDY THE EFFECT OF EXOGENOUS AND ENDOGENOUS IRISIN ON OBESITY AND TYPE II DIABETES MELLITUS IN MALE ALBINO RATS

  • Medical Physiology Department, Faculty of Medicine, Tanta University, Egypt.
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Irisin is a myokine secreted from muscle cells and other organs and it has multiple endocrinal effects on other body systems. The exact relationship of irisin in diabetes and obesity is still not completely understood. Aim of the work: Is to study the effect of exogenous and endogenous irisin on obesity and type II diabetes mellitus in male albino rats. Methods: 90 male albino rats divided into 3 groups. Control group;10 rats that fed with a regular diet. Obese group; 40 rats that fed with high fat diet for 8 weeks then subdivided into 4 equal groups 10 rats each. Control obese group; treated by intraperitoneal (ip) injection of 150 μl saline daily for 8 weeks. Irisin treated obese group;treated by ip injection of 150 μl of prepared irisin solution daily for 8 weeks. Exercise treated obese group;treated by moderate intensity swimming exercise for 30 min per day 5 days a week for 8 successive weeks. Irisin and exercise treated obese group;treated as before. Diabetic group; 40 rats that fed with high fat diet for 4 weeks then injected with a single ip streptozotocin (STZ) in a dose of 30 mg/kg body weight. After one week, diabetic group subdivided into 4 equal groups 10 rats each. Control diabetic group, irisin treated diabetic group, exercise treated diabetic group and irisin and exercise treated diabetic group;treated as before. Results:Non treated obese and diabetic groups showed significant increase in body weight gain, body mass index, serum insulin level, fasting glucose level,(HOMA-IR), osteopontin level, triglycerides level and atherogenic index of plasma.While, showed significant decrease in serum nitrite/ nitrate level,HDL cholesterol level,irisin level and (HOMA-S) when compared to the control group.In contrast, irisin treated obese and diabetic groups showed significant decrease in body weight gain, body mass index, serum insulin level, fasting glucose level,(HOMA-IR), osteopontin level, triglycerides level and atherogenic index of plasma. Whileit showed significant increase in serum nitrite/ nitrate level, HDL cholesterol level, irisin level and (HOMA-S) when compared to the control obese and control diabetic groups respectively.Treated obese and diabetic groups by moderate intensity swimming exercise for 8 successive weeks showed; significant changes in all parameters as compared to control obese and control diabetic groups respectively and insignificant changes in all parameters as compared to irisin treated groups.Combination of irisin and exercise treated obese and diabetic groups showed insignificant change compared to control group and a significant change compared to either irisin treated groups or exercise treated groups. except in body weight gain and body mass index there is no significant difference as compared to control group. Our work also showed that; serum irisin level is negatively correlated with all studied parameters except; insulin sensitivity, serum HDL cholesterol level and serum nitrite/nitrate level is positively correlated.We can conclude that combination therapy of irisin and exercise produce better results as anti hyperglycemic, anti-hyperlipidemic and , antioxidant.

  1. Abd Al-Aleem D. and Moursi S. (2017): Effect of Exercise on the Interplay between Serum Irisin and Some Metabolic and Hemostatic Parameters in Obesity Rat Model. Med. J. Cairo Univ., 85, (5): 1653-1667.
  2. Ahmad R.,?Al-Mass A.,?Al-Ghawas D.,?Shareif N., ?Zghoul N., et al. (2013): Interaction of Osteopontin with IL-18 in Obese Individuals: Implications for Insulin Resistance. PLoS One.; 8(5): e63944.
  3. Alencar J.P., Prado F.M., Coelho M.B., Raissa M.R, Jos? A.N., and Ivana R.R. (2017): Low Irisin Levels in Patients with Type 2 Diabetes Mellitus without Current Treatment:a Systematic Review. International archives of Medicinesection: endocrinology ISSN: 1755-7682 Vol. 10 No. 171.and endothelial function in lean and obese subjects. Clin Endocrinol (Oxf) 83: 339?343.
  4. Basil O., Maysaa J. and Ghassan M. (2014):Irisin impact as a medication that ameliorate and hinder the development of insulin resistance associated disorders without regular exercise (experimental study).Journal of Dental and Medical Sciences. 13,(9): 28-35.
  5. Bhowmik, B., Siddiquee T., Mujumder A., Afsana F., Ahmed T., Mdala A., et al. (2018): Serum lipid profile and its association with diabetes and prediabetes in a rural bangladeshi population. international journal of environmental research and public health,15(9), 1944.
  6. Bird and Hawley A. (2017): Update on the effects of physical activity on insulin sensitivity in humans. BMJ open sport & exercise medicine, 2(1), e000143.
  7. Bostr?m P., Wu J., Jedrychowski P., Korde A., Ye L., et al. (2012): A PGC1- α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature481, 463?468.
  8. Chen C. A., Druhan L. J., Varadharaj S., Chen Y. R. and Zweier J. L. (2008):Phosphorylation of endothelial nitric-oxide synthase regulates superoxide generation from the enzyme. The Journal of biological chemistry, 283(40), 27038?27047.
  9. Choi Y.K.,?Kim M.K.,?Bae K.H.,?Seo H.A.,?Jeong J.Y.,?Lee W.K.,?Kim J.G.,?Lee I.K. and ?Park K.G.( 2013): irisin levels in new-onset type 2 diabetes. Diabetes Research; p. 96-101.
  10. Czech M. P. (2017): Insulin action and resistance in obesity and type 2 diabetes. Nature medicine, 23(7), 804?814.
  11. da Rocha L., Crisp A. H., de Oliveira M. R., da Silva C. A., Silva J. O., et al. (2016):Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats. TheScientificWorldJournal, 2016, 2194120.
  12. Dobi?sov? M.?(2004):?Atherogenic Index of Plasma [log(triglyceride/HDL-Cholesterol)]: Theoretical and Practical Implications. Chem.,?50: 1113-1115.
  13. Dyakova Y., Kapilevich L. V., Shylko V. G., Popov S. V. and Anfinogenova Y. (2015):Physical exercise associated with NO production: signaling pathways and significance in health and disease. Frontiers in cell and developmental biology, 3, 19.
  14. Ercan B., Umit Z., Ebru G. G., Bahar Y. O., Faruk C., et al. (2018):Effects of Irisin and Exercise on Metabolic Parameters and Reproductive Hormone Levels in High-Fat Diet-Induced Obese Female MiceReproductive Sciences, 25(2): 281-291.
  15. Fang H.,,Ningning H.,Di W. and Xiaodong S. (2015):Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway. Am J Physiol Heart Circ Physiol 309: H1501?H1508.
  16. Fu J., Han Y., Wang J., Liu Y., Zheng S., Zhou L., Jose P.A. and Zeng C. (2016):Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK-Akt-eNOS-NO Pathway in the Spontaneously Hypertensive Rat. J Am Heart Assoc. 26;5(11): e003433.
  17. Gao, Lin Z. Liu Y., et al. (2018): Hypolipidemic effect of FragarianilgerrensisSchlecht. medicine compound on hyperlipidemic rats; Lipids in Health and Disease.17: 222.
  18. Ghanbari, Nejati V. and Khazaei, M. (2016): Improvement in Serum Biochemical Alterations and Oxidative Stress of Liver and Pancreas following Use of Royal Jelly in Streptozotocin-Induced Diabetic Rats. Cell journal, 18(3): 362?370.
  19. Grove T.H. (1979):Effect of reagent pH on determination of high-density lipoprotein cholesterol by precipitation with sodium phosphotungstate-magnesium. Chem., 25 (4): 560-564.
  20. Guilherme F. F. S., Marisa C. R., Fernanda O. D., et al. (2012): The effects of exercise modalities on adiposity in obese rats.Clinics;67(12):1469-1477.
  21. Han F., Zhang S., Hou N., Wang D. and Sun X. (2015):Irisin improves endothelial function in obese mice through the AMPK‐eNOS pathway. Am J Physiol Heart Circ Physiol.;309:H1501?H1508.
  22. Hashem M., Nasr El-Deen N. and Ghareeb O. (2018): Biochemical Effects Of Ginger And/Or Green Tea Extracts In High Fat Diet- Induced Obese Rats. Slov Vet Res; 55:241-249.
  23. He, Li J., Liu Z., Chuang C. C., Yang W. and Zuo L. (2016): Redox Mechanism of Reactive Oxygen Species in Exercise. Frontiers in physiology, 7: 486.
  24. He W., Bai Q., La A., Tang C. and Zang A. (2015): Irisin levels are associated with urotensin levels in diabetic patients. J Diabetes Invest Vol. 6 No.5,
  25. Huh J.Y., Panagiotou G., Mougios V., Brinkoetter M., Vamvini M.T., Schneider B.E. and Mantzoros C.S. (2012):FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism61: 1725?1738.
  26. Hye J. L., Jung O. L., Nami K., et al.( 2015):Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK. Molecular Endocrinology, 29, (6): 873?881.
  27. Irving, B.A., Still, C.D. and Argyropoulos, G. (2014):Does IRISIN Have a BRITE Future as a Therapeutic Agent in Humans?.CurrObes3(2): 235?241.
  28. Kahles F., Findeisen H. M. and Bruemmer D. (2014): Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes. Molecular metabolism, 3(4): 384?393.
  29. Kamei N., Tobe K., Suzuki R., Ohsugi M., Watanabe T., et al. (2006): Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem.;281(36):26602-26614.
  30. Kao P.C., Taylor R.L. and Service F.J. (1994): Proinsulin by Immunochemiluminometric Assay for the Diagnosis of Insulinoma. Jorunal of Clin Endocrinol Metab; 78 (5): 1048-1051.
  31. Khadke S.P., Kuvalekar A.A., Harsulkar A.M. and Mantri N. (2019):High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes. Biomedicines, 7(4):76.
  32. Kiefer F.W., Zeyda M., Todoric J., Huber J., Geyeregger R., Weichhart T., et al. (2008): Osteopontin expression in human and murine obesity: Extensive local up-regulation in adipose tissue but minimal systemic alterations. Endocrinology, 149: 1350?1357.
  33. Kohl T.O. and Ascoli C.A.(2017):Immunometric Double-Antibody Sandwich Enzyme-Linked Immunosorbent Assay. Cold Spring Harb Protoc.;2017(6):pdb.Prot093724.
  34. Korta, Pocheć E. and Mazur-Biały A. (2019):Irisin as a Multifunctional Protein: Implications for Health and Certain Diseases. Medicina.; 55(8):485.
  35. Kyung H., Park, L. Z., Mary B., Bindiya T., Ayse ., Kyoung E. J., Michael A. T., Eleni V. G.i, Joo Y. H., Fadime D., Cynthia R. D., Judith A. C., Christos S. M.(2013): Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome. The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 12, 1, Pages 4899?4907
  36. Liu J.J., Wong M.D., Toy W.C., Tan C.S., Liu S., Ng X.W., Tavintharan S., Sum C.F., Lim S.C.( 2013):Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complications.;27(4),365?369.
  37. Liu S., Du F., Li X.,Wang M., Duan R., Zhan J., Wu Y. and Zhang Q. (2017): Effects and underlying mechanism of irisin on the proliferation and apoptosis of pancreatic β cells. PLoS ONE 12(4): e0175498.
  38. Liu T.Y., Shi C.X., Gao R., Sun H.J., Xiong X.Q., Ding L., et al. (2015): Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clin Sci (Lond).; 129: 839?850.
  39. Lu Y., Li H., Shen S. W., Shen Z. H., Xu M., Yang C. J., et al. (2016): Swimming exercise increases serum irisin level and reduces body fat mass in high-fat-diet fed Wistar rats. Lipids in health and disease, 15: 93.
  40. Matthews D.R., Hosker J.P., Rudenski A.S., Naylor B.A., Treacher D.F. and Turner R.C. (1985): Homeostasis model assessment: insulin resistance and beta-cell functionfrom fasting plasma glucose and insulin concentrations in man. Diabetologia; 28:412-19.
  41. Mazur-BialyI., Bilski J., Pochec E. and Brzozowski T.( 2017):New insight into the direct anti-inflammatory activity of a myokine irisin against proinflammatory activation of adipocytes. Implication for exercise in obesity. J PhysiolPharmacol. 68(2):243-251.
  42. Mcgowan M.W., Artiss J.D.,?Strandbergh D.R. and?Zak B., (1983): A?peroxidase-coupled?method?for the colorimetric determination of?serum?triglycerides.Clin Chem; 29 (3):538-542.
  43. Mehrabian S.,Taheri E., Karkhaneh M., Qorbani M. and Hosseini S. (2016):Association of circulating irisin levels with normal weight obesity, glycemic and lipid profile. Journal of Diabetes & Metabolic Disorders (15:17)
  44. Montgomery H.A. and Dymock J.F. (1961):Colorimetric determination of nitric oxide. In Analyst; 86-414.
  45. Moreno-Navarrete J.M., Ortega F., Serrano M., Guerra E., Pardo G., Tinahones F., et al.(2013): Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab.; 98(4): 769?778.
  46. Moustafa H. and Marwa A. (2017): Effect of Swimming Exercise on Irisin Levels in Streptozotocin Induced Type 1 and Type 2 Diabetes Mellitus in Rats.Med. J. Cairo Univ., Vol. 85, No. 7, December: 2625-2634.
  47. Pandey G., Shihabudeen M. S., David H. P., Thirumurugan E. and Thirumurugan K. (2015): Association between hyperleptinemia and oxidative stress in obese diabetic subjects. Journal of diabetes and metabolic disorders. (14)14-24.
  48. Pardo M., Crujeiras A. B., Amil M., et al. (2014): Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index. International Journal of Endocrinology.;2014: 857270.
  49. Pedersen B.K., Febbraio M.A.(2012): Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nature Reviews. Endocrinology; 8:457?465.
  50. P?sa A., Szab? R., Kupai K., Csonka A., Szalai Z., Veszelka M., et al. (2015): Exercise training and calorie restriction influence the metabolic parameters in ovariectomized female rats. Oxid Med Cell Longev., 2015:787063.
  51. Sabitha V., Ramachandran S., Naveen K.R. and Panneerselvam K.(2011):Antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus (L.) Moench. In streptozotocin induced diabetic rats. J Pharm Bioallied Sci3:397?402.
  52. E. and?Hill B.G. (2014):Regulation Of Obesity And Insulin Resistance By Nitric Oxide. Free Radic Biol Med. 73: 383?399.
  53. Seo D., Kwak H., Lee S., Cho Y., Song I., Kim N., Bang H., Rhee B., Ko K., Park B. and Han? (2014): Effects of aged garlic extract and endurance exercise on skeletal muscle? FNDC-5? and? circulating? irisin? in? high- fat-diet rat models. Nutr. Res. Pract., 8: 177-82,.
  54. Shaw J., Sicree R. and Zimmet P. (2010):Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract.; p 4-14.
  55. Skovs? S. (2014): Modeling type 2 diabetes in rats using high fat diet and streptozotocin. Journal of diabetes investigation, 5(4): 349?358.
  56. Summermatter S., Shui G., Maag D., Santos G., Wenk M. R. and Handschin C. (2013): PGC-1α improves glucose homeostasis in skeletal muscle in an activity-dependent manner. Diabetes, 62(1): 85?95.
  57. Tietz N.W., (1986):Determination of blood glucose. Text book of clinical chemistry WB Saunders, Philadelphia; 796.
  58. Vincent, Thakkar H., Aggarwal S., Mridha A. R., Ramakrishnan L. and Singh, A. (2019): ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity. Diabetes, metabolic syndrome and obesity : targets and therapy, 12: 275?284.
  59. Wang B., Yu Y. and Han L. (2012): Adiponectin improves endothelial dysfunction caused by elevated FFAs levels, partially through cAMP-dependent pathway. Diabetes Res Clin Pract 97: 119?124.
  60. Wang Y. and Xu D. (2017):Effects of aerobic exercise on lipids and lipoproteins.?Lipids in health and disease,?16(1): 132.
  61. Xiong X.Q., Chen D., Sun H.J., Ding L., Wang J.J., Chen Q., et al. (2015):FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity. Biochim et Biophysica Acta.1852 (9):1867?1875.

[Hanan Mostafa Abdallah, Sahar Ahmed Elsawy, Abeer Abed Ahmed and Rizk Mahmoud Elkholy (2020); STUDY THE EFFECT OF EXOGENOUS AND ENDOGENOUS IRISIN ON OBESITY AND TYPE II DIABETES MELLITUS IN MALE ALBINO RATS Int. J. of Adv. Res. 8 (May). 156-171] (ISSN 2320-5407). www.journalijar.com

Hanan Mostafa Abdallah
Medical Physiology Department, Faculty of Medicine, Tanta University, Egypt

DOI:

Article DOI: 10.21474/IJAR01/10916      
DOI URL: https://dx.doi.org/10.21474/IJAR01/10916

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