Effect of Aerobic Training with Aqueous Allium sativum L on IL-17, IL-22 Expression and Insulin Resistance in Diabetic Rats

Document Type : original article

Authors

Department of Physical Education and Sport Science, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran

Abstract

Background and Purpose: There is now mounting evidence that pro-inflammatory pathways, which are mediated by T cells (that secrete IL-17 and IL-22), play a critical role in metabolic control. The aim of this study was to examine the effect of aerobic training along with aqueous extract of Garlic (Allium sativum L.) on relative expression of IL-17, IL-22 and insulin resistance in streptozotocin-diabetic rats.
Materials and Methods: In this experimental study, 40 male Wistar rats (age five weeks and weight 162.12 ± 15.24 g) were obtained from the Pasteur Institute and transferred to the laboratory. After transferring the rats to the laboratory, inducing diabetes and familiarizing them with exercise on a rodent treadmill, they were randomly divided into five groups: Control-Normal (CN), Diabetes (DM), Diabetes-Training (TDM), Diabetes-Garlic (GDM) and Diabetes-Training-Garlic (TGDM). Diabetes was induced in the rats by the intraperitoneal administration of a single dose of Streptozotocin (60 mg/kg). Blood glucose of 250 mg/dL was the criterion for diabetic rats. Training groups have performed an aerobic running program (at 10-18 m/min, 10-40 min/day, and five days/week) on a motor-driven treadmill for eight weeks. A dose of one ml of garlic extract /100 g body weight (about 0.4 grams per 100 grams of body weight) was orally administered daily to rats. The expression of IL-17 and IL-22 was measured by RT-PCR method. After estimating fasting glucose and insulin levels, HOMA-IR index was used to evaluate insulin resistance. Data were analyzed using ANOVA and Pearson's correlation coefficient at P < 0.05.
 
Results: The expression of IL-17 (P = 0.0001), IL-22 (P = 0.0001) and HOMA-IR level (P = 0.0001) increased in DM groups compared to CN group. IL-17, IL-22 and HOMA-IR was significantly lower in TDM (respectively, P = 0.008, P = 0.040, P = 0.0001), GDM (respectively, P = 0.017, P = 0.044, P = 0.0001) and TGDM (respectively, P= 0.0001, P = 0.0001, P = 0.0001) groups than in DM group. Also, IL-17 and IL-22 in the TGDM group lower than TDM (respectively, P = 0.045, P= 0.041) and GDM (respectively, P = 0.023, P = 0.038) groups. A positive correlation was observed between HOMA-IR and IL-17 (P = 0.0001) and IL-22 (P = 0.001).
Conclusions: The findings of the present study show that probably the increase in the relative expression of IL-17 and IL-22 with the induction of diabetes is associated with an increase in insulin resistance. Decreased IL-17 and IL-22 expression adipose tissue followed by aerobic training and aqueous garlic extract were associated with decreased HOMA-IR in diabetic rats. In addition, the combination of aerobic exercise with garlic extract had synergistic effects and reduced inflammation and HOMA-IR compared to each alone. Since diabetics are constantly exposed to inflammation and according to the reduction of IL-17 and IL-22 following aerobic exercise and consumption of garlic extract, the use of these two could possibly be of therapeutic importance for T2DM patients.

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References

  1. Cornier M-A, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic syndrome. Endocrine reviews. 2008;29(7):777-822.
  2. Frostegård J. Immune mechanisms in atherosclerosis, especially in diabetes type 2. Frontiers in Endocrinology. 2013;4:162.
  3. Fabbrini E, Cella M, Mccartney SA, Fuchs A, Abumrad NA, Pietka TA, et al. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013;145(2):366-74. e3.
  4. Ip B, Cilfone NA, Belkina AC, DeFuria J, Jagannathan‐Bogdan M, Zhu M, et al. Th17 cytokines differentiate obesity from obesity‐associated type 2 diabetes and promote TNF α production. Obesity. 2016;24(1):102-12.
  5. Roohi A, Tabrizi M, Abbasi F, Ataie-Jafari A, Nikbin B, Larijani B, et al. Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls. BioMed research international. 2014;2014.
  6. Abdel-Moneim A, Bakery HH, Allam G. The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomedicine & Pharmacotherapy. 2018;101:287-92.
  7. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annual review of immunology. 2011;29:71-109.
  8. Hasnain SZ, Borg DJ, Harcourt BE, Tong H, Sheng YH, Ng CP, et al. Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. Nature medicine. 2014;20(12):1417-26.
  9. Gong F, Wu J, Zhou P, Zhang M, Liu J, Liu Y, et al. Interleukin-22 might act as a double-edged sword in type 2 diabetes and coronary artery disease. Mediators of inflammation. 2016; 2016:8254797.
  10. Malin SK, Finnegan S, Fealy CE, Filion J, Rocco MB, Kirwan JP. β-Cell dysfunction is associated with metabolic syndrome severity in adults. Metabolic syndrome and related disorders. 2014;12(2):79-85.
  11. Mirzendedel z, attarzadehoseini s, bijeh N, raouf saeb Aa. A Comparison of the Effects of Twelve Weeks Combined Training with Different Ordering on CTRP3, TNF-α, IL6 and Insulin Resistance in Women with Type 2 Diabetes. Iranian Journal of Endocrinology and Metabolism. 2019;21(4):203-16. (In Persian.)
  12. Alvarenga-Filho H, Sacramento PM, Ferreira TB, Hygino J, Abreu JEC, Carvalho SR, et al. Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators. Journal of neuroimmunology. 2016;293:91-9.
  13. Avandi SM, Zahedi M. The effects of eight weeks’ yoga training on serum levels of IL-17 in women with multiple sclerosis. Journal of Sport and Exercise Physiology. 2019;12(2):81-92.
  14. Ramos JS, Dalleck LC, Stennett RC, Mielke GI, Keating SE, Murray L, et al. Effect of Different Volumes of Interval Training and Continuous Exercise on Interleukin-22 in Adults with Metabolic Syndrome: A Randomized Trial. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2020;13:2443.
  15. AliKhazaei H, Jalili A, Gilani SRM, Alidadi A, Moulaei N, Haghighi J, et al. The Effect of 8 Weeks Aerobic Training on Serum Levels of Pro-inflammatory Cytokines (IL-17) and Immunoglobulins (IgA, IgM, IgG and IgE) Levels in Patients with Type 2 Diabetes. Annals of Medical and Health Sciences Research. 2018; 8:376-379.
  16. Francois ME, Little JP. Effectiveness and safety of high-intensity interval training in patients with type 2 diabetes. Diabetes Spectrum. 2015;28(1):39-44.
  17. Orsatti FL, Nahas EA, Maesta N, Nahas-Neto J, Burini RC. Plasma hormones, muscle mass and strength in resistance-trained postmenopausal women. Maturitas. 2008;59(4):394-404.
  18. Pedraza-Chaverri J, Yam-Canul P, Chirino YI, Sánchez-González DJ, Martínez-Martínez CM, Cruz C, et al. Protective effects of garlic powder against potassium dichromate-induced oxidative stress and nephrotoxicity. Food and chemical toxicology. 2008;46(2):619-27.
  19. Moutia M, Seghrouchni F, Abouelazz O, Elouaddari A, Al Jahid A, Elhou A, et al. Allium sativum L. regulates in vitro IL-17 gene expression in human peripheral blood mononuclear cells. BMC complementary and alternative medicine. 2016;16(1):1-10.
  20. Sivam GP. Protection against Helicobacter pylori a nd Other Bacterial Infections by Garlic. The Journal of nutrition. 2001;131(3):1106S-8S.
  21. Ota N, Takano F, Muroga S, Kawabata T, Ishigaki Y, Yahagi N, et al. Garlic extract and its selected organosulphur constituents promote ileal immune responses ex vivo. Journal of Functional Foods. 2012;4(1):243-52.
  22. Ried K, Travica N, Sali A. The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: the AGE at Heart trial. Integrated blood pressure control. 2016;9:9.
  23. Falahatian S, Haddad R, Pakravan N. Modulatory effects of R10 fraction of garlic (Allium sativum L.) on hormonal levels, T cell polarization, and fertility-related genes in mice model of polycystic ovarian syndrome. Journal of Ovarian Research. 2022;15(1):1-10.
  24. Hosseini SE, Karimzadeh K. Anti-diabetic effects of hydroalcohlic juglans regia male flower extract on blood glucose level and on liver enzymes activity in intact and diabetogenized adult male rat. Journal of Birjand University of Medical Sciences. 2012;19(2):165-72. (In Persian).
  25. Chae C-H, Jung S-L, An S-H, Jung C-K, Nam S-N, Kim H-T. Treadmill exercise suppresses muscle cell apoptosis by increasing nerve growth factor levels and stimulating p-phosphatidylinositol 3-kinase activation in the soleus of diabetic rats. Journal of physiology and biochemistry. 2011;67(2):235-41.
  26. El-Demerdash F, Yousef MI, El-Naga NA. Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats. Food and chemical toxicology. 2005;43(1):57-63.
  27. Abbasi F, Amiri P, Sayahpour FA, Pirmoradi S, Abolhalaj M, Larijani B, et al. TGF-β and IL-23 gene expression in unstimulated PBMCs of patients with diabetes. Endocrine. 2012;41(3):430-4.
  28. Zhao R, Tang D, Yi S, Li W, Wu C, Lu Y, et al. Elevated peripheral frequencies of Th22 cells: a novel potent participant in obesity and type 2 diabetes. PloS one. 2014;9(1):e85770.
  29. Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I, Aron-Wisnewsky J, et al. T cell–derived IL-22 amplifies IL-1β–driven inflammation in human adipose tissue: Relevance to obesity and type 2 diabetes. Diabetes. 2014;63(6):1966-77.
  30. Zeng C, Shi X, Zhang B, Liu H, Zhang L, Ding W, et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. Journal of molecular medicine. 2012;90(2):175-86.
  31. Guo H, Xu BC, Yang XG, Peng D, Wang Y, Liu XB, et al. A High Frequency of Peripheral Blood IL‐22+ CD4+ T Cells in Patients With New Onset Type 2 Diabetes Mellitus. Journal of Clinical Laboratory Analysis. 2016;30(2):95-102.
  32. Xu R, Tao A, Zhang S, Zhang M. Neutralization of interleukin-17 attenuates high fat diet-induced non-alcoholic fatty liver disease in mice. Acta Biochim Biophys Sin. 2013;45(9):726-33.
  33. Abdi A, sheykholeslami z, Ghorbani hasan saraee A, abaszadeh h, farzanegi p, sheykholeslami z. Effects of aerobic training with coriander seed extract on serum paraoxonase-1, TNF-α, and CRP in diabetic rats. Journal Of Neyshabur University Of Medical Sciences. 2018;6(1):70-80. (In Persian).
  34. Rashet A, Abdi A. The Effect of Aerobic Exercise and Capsaicin on the Gene Expression of Pancreaticpdx1 and GLUT2 in Rats Fed High-Fat Diet. Iranian Journal of Diabetes and Lipid Disorders. 2021;21(2):101-10. (In Persian).
  35. Nani D, Proverawati A. Immunomodulatory effects of black solo garlic (Allium sativum L.) on streptozotocin-induced diabetes in Wistar rats. Heliyon. 2021;7(12):e08493.
  36. Yang G, Li S, Li B, Cheng L, Jiang P, Tian Z, et al. Protective effects of garlic-derived S-allylmercaptocysteine on IL-1β-stimulated chondrocytes by regulation of MMPs/TIMP-1 ratio and type II collagen expression via suppression of NF-κB pathway. BioMed Research International. 2017; 2017:8686207.
  37. Lee DY, Li H, Lim HJ, Lee HJ, Jeon R, Ryu J-H. Anti-inflammatory activity of sulfur-containing compounds from garlic. Journal of medicinal food. 2012;15(11):992-9.
  38. Miki S, Inokuma Ki, Takashima M, Nishida M, Sasaki Y, Ushijima M, et al. Aged garlic extract suppresses the increase of plasma glycated albumin level and enhances the AMP‐activated protein kinase in adipose tissue in TSOD mice. Molecular nutrition & food research. 2017;61(5):1600797.
  39. Miki S, Suzuki JI, Kunimura K, Morihara N. Mechanisms underlying the attenuation of chronic inflammatory diseases by aged garlic extract: Involvement of the activation of AMP‑activated protein kinase. Experimental and Therapeutic Medicine. 2020 Feb;19(2):1462-1467.
  40. Enayatjazi M, Esfarjani F, Reisi J, Moshtaghian SJ. Studying the effect of garlic consumption and endurance training on serum levels of some pro-and anti-inflammatory cytokines in female mice with breast cancer-A randomized trial. International Journal of Preventive Medicine. 2022; 12;13:38.
  41. Mohammadi Sarableh N, Tahmasebi W, Azizi M, Abdullahzad H. The effect of eight weeks of progressive resistance training with garlic supplementation on serum levels of C-reactive protein and insulin resistance in overweight women. Journal of Sport and Exercise Physiology. 2022;15(3):46-56. (In Persian).

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History

  • Receive Date: 30 July 2022
  • Revise Date: 23 August 2022
  • Accept Date: 25 January 2023
  • First Publish Date: 21 February 2023
  • Publish Date: 21 March 2023

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