Effects of Lipoic Acid and High-Intensity Interval Training (HIIT) on Pancreatic VEGFR-3 Levels in Diabetic Rat Model

Hashemian Esfahani, Seyed Ramin; Dadban Shahamat, Minoo; Askari, Asra; Nezhadebrahimi, Abbas

doi:10.18502/ijdo.v16i2.15709

Volume 16, Issue 2 (volume 16, number 2 2024) IJDO 2024, 16(2): 103-111 | Back to browse issues page

‎ 10.18502/ijdo.v16i2.15709

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Hashemian Esfahani S R, Dadban Shahamat M, Askari A, Nezhadebrahimi A. Effects of Lipoic Acid and High-Intensity Interval Training (HIIT) on Pancreatic VEGFR-3 Levels in Diabetic Rat Model. IJDO 2024; 16 (2) :103-111
URL: http://ijdo.ssu.ac.ir/article-1-873-en.html

Effects of Lipoic Acid and High-Intensity Interval Training (HIIT) on Pancreatic VEGFR-3 Levels in Diabetic Rat Model

Seyed Ramin Hashemian Esfahani

, Minoo Dadban Shahamat ^*

, Asra Askari

, Abbas Nezhadebrahimi

Department of Physical Education, Azadshahr Branch, Islamic Azad University, Azadshahr, Iran.

Abstract: (46 Views)

Objective: The purpose of this experimental research is to investigate the effects of High-Intensity Interval Training (HIIT) and Lipoic Acid )ALA( supplementation on VEGFR-3 of pancreatic in diabetic Wistar rats model.
Materials and Methods: 20 male Wistar rats weighing 159 ± 3 gr and aged3 weeks, were randomly assigned into 4 groups:1) diabetes/sham, 2)diabetes/ ALA, 3)diabetes/exercise/sham, and 4) diabetes /exercise/ ALA. Diabetes was induced with streptozotocin (65 mg/kg dose) and Nicotinamide (120 mg/kg dose). After two weeks of familiarization with interval training, the rats started their main training, included 10 repetitions of 4 minutes of running on the treadmill with an intensity of 85-90% VO2max and 2 minutes of active rest between repetitions (5-10 m/min) for 5 sessions per week for 6 weeks. ALA supplement was taken at a dose of 20 mg/kg/day for 6 weeks. One-way ANOVA test used and Tukey's post hoc test at for analysis (P≤ 0.05).
Results: HIIT has a significant effect on blood glucose (P= 0.004) and insulin (P= 0.001) and VEGFR3 (P= 0.001) of pancreatic tissue of diabetic rats.
Conclusion: Lymphatic vessels play an important role in the pancreas and treat diabetes.The results of this research showed that HIIT and ALA increased lymphangiogenesis in the diabetic rat model.

Keywords: ALA, HIIT, Lymph angiogenesis, Diabetic model rats

Full-Text [PDF 478 kb] (35 Downloads)

Type of Study: Research | Subject: Special
Received: 2023/11/23 | Accepted: 2024/04/6 | Published: 2024/06/21

References

1. Creager MA, Matsushita K, Arya S, Beckman JA, Duval S, Goodney PP, et al. Reducing nontraumatic lower-extremity amputations by 20% by 2030: time to get to our feet: a policy statement from the American Heart Association. Circulation. 2021;143(17):e875-91.

2. Scallan JP, Hill MA, Davis MJ. Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling. Cardiovascular research. 2015;107(1):89-97.

3. Oliver G. Lymphatic vasculature development. Nature Reviews Immunology. 2004;4(1):35-45.

4. Oliver G, Kipnis J, Randolph GJ, Harvey NL. The lymphatic vasculature in the 21st century: novel functional roles in homeostasis and disease. Cell. 2020;182(2):270-96.

5. Petrova TV, Koh GY. Organ-specific lymphatic vasculature: from development to pathophysiology. Journal of Experimental Medicine. 2018;215(1):35-49.

6. Roost MS, van Iperen L, de Melo Bernardo A, Mummery CL, Carlotti F, de Koning EJ, et al. Lymphangiogenesis and angiogenesis during human fetal pancreas development. Vascular cell. 2014;6:1-11.

7. Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, et al. Pancreatic islet production of vascular endothelial growth factor-a is essential for islet vascularization, revascularization, and function. Diabetes. 2006;55(11):2974-85.

8. Stacker SA, Stenvers K, Caesar C, Vitali A, Domagala T, Nice E, et al. Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers. Journal of Biological Chemistry. 1999;274(45):32127-36.

9. Kajiya K, Detmar M. An important role of lymphatic vessels in the control of UVB-induced edema formation and inflammation. Journal of Investigative Dermatology. 2006;126(4):920-2.

10. Madsen SM, Thorup AC, Overgaard K, Jeppesen PB. High intensity interval training improves glycaemic control and pancreatic β cell function of type 2 diabetes patients. PloS one. 2015;10(8):e0133286.

11. Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, et al. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. Journal of applied physiology. 2011;111(6):1554-60.

12. Rahbar S, Naimi SS. The effect of combined aerobic and resistance exercise on biochemical factors in patients with type 2 diabetes mellitus. Journal of Research in Rehabilitation Sciences. 2018;14(4):230-8.

13. Vali Zadeh S, Motamedi P, Karami H, Rajabi H. The effects of endurance training on gene expression of VEGF and VEGFR2 of cardiac tissue in Type 2 diabetic male wistar. Journal of Arak University of Medical Sciences. 2018;21(6):107-18.(in Persian)

14. Lee SG, Lee CG, Yun IH, Hur DY, Yang JW, Kim HW. Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina. Clinical & experimental ophthalmology. 2012;40(1):e47-57.

15. Hale LJ, Hurcombe J, Lay A, Santamaría B, Valverde AM, Saleem MA, et al. Insulin directly stimulates VEGF-A production in the glomerular podocyte. American journal of physiology-Renal physiology. 2013;305(2):F182-8.

16. Liang S, Zhao T, Xu Q, Duan J, Sun Z. Evaluation of fine particulate matter on vascular endothelial function in vivo and in vitro. Ecotoxicology and Environmental Safety. 2021;222:112485.

17. Shin KO, Bae JY, Woo J, Jang KS, Kim KS, Park JS, et al. The effect of exercise on expression of myokine and angiogenesis mRNA in skeletal muscle of high fat diet induced obese rat. Journal of Exercise Nutrition & Biochemistry. 2015;19(2):91. [DOI:10.5717/jenb.2015.15061006]

18. Amri J, Parastesh M, Sadegh M, Latifi SA, Alaee M. High-intensity interval training improved fasting blood glucose and lipid profiles in type 2 diabetic rats more than endurance training; possible involvement of irisin and betatrophin. Physiology international. 2019;106(3):213-24.

19. Holmes A, Coppey LJ, Davidson EP, Yorek MA. Rat models of diet-induced obesity and high fat/low dose streptozotocin type 2 diabetes: effect of reversal of high fat diet compared to treatment with enalapril or menhaden oil on glucose utilization and neuropathic endpoints. Journal of diabetes research. 2015;2015.

20. Dworacka M, Chukanova G, Iskakova S, Kurmambayev Y, Wesołowska A, Frycz BA, et al. New arguments for beneficial effects of alpha-lipoic acid on the cardiovascular system in the course of type 2 diabetes. European Journal of Pharmaceutical Sciences. 2018;117:41-7.

21. Costigan SA, Eather N, Plotnikoff RC, Taaffe DR, Lubans DR. High-intensity interval training for improving health-related fitness in adolescents: a systematic review and meta-analysis. British journal of sports medicine. 2015;49(19):1253-61.

22. Leandro Cg, Levada Ac, Hirabara Sm, Manhas-De-Castro Ra, De-Castro Cb, Curi R, Pithon-Curi Tc. Aprogram Of Moderate Physical Training For Wistar rats based on maximal oxygen consumption. The Journal of Strength & Conditioning Research. 2007;21(3):751-6. [DOI:10.1519/00124278-200708000-00016]

23. Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. The Journal of Biochemistry. 2013;153(1):13-9.

24. Cumsille P, Coronel A, Conca C, Quiñinao C, Escudero C. Proposal of a hybrid approach for tumor progression and tumor-induced angiogenesis. Theoretical biology and medical modelling. 2015;12:1-22.

25. Westermeier F, Salomón C, González M, Puebla C, Guzmán-Gutiérrez E, Cifuentes F, et al. Insulin restores gestational diabetes mellitus-reduced adenosine transport involving differential expression of insulin receptor isoforms in human umbilical vein endothelium. Diabetes. 2011;60(6):1677-87.

26. Du J, Wang Y, Tu Y, Guo Y, Sun X, Xu X, et al. A prodrug of epigallocatechin-3-gallate alleviates high glucose-induced pro-angiogenic factor production by inhibiting the ROS/TXNIP/NLRP3 inflammasome axis in retinal Müller cells. Experimental Eye Research. 2020;196:108065.

27. Lim HY, Thiam CH, Yeo KP, Bisoendial R, Hii CS, McGrath KC, et al. Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-mediated transport of HDL. Cell metabolism. 2013;17(5):671-84.

28. Singla B, Aithabathula RV, Kiran S, Kapil S, Kumar S, Singh UP. Reactive oxygen species in regulating lymphangiogenesis and lymphatic function. Cells. 2022;11(11):1750.

29. Niessen K, Zhang G, Ridgway JB, Chen H, Yan M. ALK1 signaling regulates early postnatal lymphatic vessel development. Blood, The Journal of the American Society of Hematology. 2010;115(8):1654-61.

30. Pytowski B, Goldman J, Persaud K, Wu Y, Witte L, Hicklin DJ, et al. Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibody. Journal of the National Cancer Institute. 2005;97(1):14-21.

31. Winder WW. Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle. Journal of applied physiology. 2001;91(3):1017-28.

32. McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 2002;51(1):7-18.

33. Ruderman N, Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nature reviews Drug discovery. 2004;3(4):340-51.

34. Ceriello A, Quagliaro L, D'Amico M, Di Filippo C, Marfella R, Nappo F, et al. Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes. 2002;51(4):1076-82.

35. Dokun AO, Chen L, Lanjewar SS, Lye RJ, Annex BH. Glycaemic control improves perfusion recovery and VEGFR2 protein expression in diabetic mice following experimental PAD. Cardiovascular research. 2014;101(3):364-72.

36. Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, et al. α-Lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochemical and biophysical research communications. 2005;332(3):885-91.

37. Ross R. Atherosclerosis-an inflammatory disease. New England journal of medicine. 1999;340(2):115-26.

38. Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005;54(1):158-65.

39. Karstoft K, Winding K, Knudsen SH, James NG, Scheel MM, Olesen J, Holst JJ, Pedersen BK, Solomon TP. Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial. Diabetologia. 2014;57:2081-93.