اثر تمرین اینتروال متوسط شدت و لیپوئیک اسید لیپوزومال بر لنف آنژیوژنز پانکراس، گلوکز و انسولین سرمی Rat‌های مدل مبتلا به دیابت

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 استادیار، گروه تربیت بدنی، واحد آزادشهر، دانشگاه آزاد اسلامی، آزادشهر، ایران

2 گروه تربیت بدنی، واحد آزادشهر، دانشگاه آزاد اسلامی، آزادشهر، ایران

3 استادیار ،گروه تربیت بدنی، واحد گرگان، دانشگاه آزاد اسلامی، گرگان، ایران

چکیده

مقدمه: لنف آنژیوژنز، نقش مهمی در التهاب جزایر و تنظیم انسولین دارد. این پژوهش، با هدف بررسی اثر تمرین اینتروال متوسط شدت و مکمل آلفالیپوئیک اسید بر Vascular endothelial growth factor receptor 3 (VEGFR3) بافت پانکراس، گلوکز و انسولین سرمی Rat‌های نر نژاد Wistar مدل مبتلا به دیابت انجام شد.روش‌ها: در یک مطالعه‌ی تجربی، 25 سر Rat نر نژاد Wistar، با میانگین سن 3 هفته و وزن 3 ± 159 گرم به پنج گروه (5 = n در هر گروه) شامل گروه شاهد سالم، دیابت + سالین، دیابت + مکمل، دیابت + تمرین + سالین، دیابت + مکمل + تمرین تقسیم شدند. القای دیابت، با تزریق داخل صفاقی استرپتوزوتوسین (65 میلی‌گرم/کیلوگرم) و نیکوتین امید (120 میلی‌گرم/کیلوگرم) انجام شد. آلفالیپوئیک اسید (Alpha lipoic acid یا ALA) به مدت 6 هفته، با دز 20 میلی‌گرم/کیلوگرم روزانه به صورت خوراکی تجویز شد. تمرین اینتروال، به مدت6 هفته، 5 جلسه در هفته شامل 13 تناوب 4 دقیقه‌ای دویدن روی تردمیل با شدت VO2max معادل 70-65 درصد و استراحت فعال بین تناوب‌ها، 2 دقیقه دویدن با شدت 10-5 متر/دقیقه بود. پس از کشتار Ratها و بافت‌برداری، بیان پروتئین VEGFR3 بافت پانکراس به روش ایمنوهیستوشیمی و گلوکز به روش کالری‌متریک و انسولین به روش enzyme-linked immunoassay (ELISA)-کالری‌متریک انجام شد. داده‌ها با آزمون One-way ANOVA و با استفاده از نرم‌افزار SPSS در سطح معنی‌داری 050/0 > P تجزیه و تحلیل شدند.یافته‌ها: 6 هفته تمرین اینتروال و تمرین اینتروال با مکمل Lysosomal acid lipase (LAL) بر VEGFR3 بافت پانکراس، گلوکز و انسولین سرمی Rat‌های مبتلا به دیابت تأثیر معنی‌داری داشت. مصرف 6 هفته مکمل LAL بر VEGFR3و انسولین سرمی Ratهای مبتلا به دیابت اثر معنی‌داری داشت.نتیجه‌گیری: تمرین اینتروال شدید و مکمل ALA باعث افزایش لنف آنژیوژنز و کاهش گلوکز خون و تغییرات مطلوب در رت‌های دیابتی شد.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect of Moderate-Intensity Interval Training (MIIT) and Liposomal Lipoic Acid on Lymphangiogenesis, Glucose, and Serum Insulin in Diabetic Rats

نویسندگان [English]

  • Minoo Dadban-Shahamat 1
  • Seyed-Ramin Hashemian-Esfahani 2
  • Asra Askari 3
1 Assistant Professor, Department of Physical Education, Azadshahr Branch, Islamic Azad University, Azadshahr, Iran
2 Department of Physical Education, Azadshahr Branch, Islamic Azad University, Azadshahr, Iran
3 Assistant Professor, Department of Physical Education, Gorgan Branch, Islamic Azad University, Gorgan, Iran
چکیده [English]

Background: Lymphangiogenesis plays an important role in islet inflammation and insulin regulation. In this study, the effect of interval training and liposomal alpha lipoic acid supplementation on serum glucose, blood insulin, and vascular endothelial growth factor receptor-3 (VEGFR3) was examined in diabetic rat.Methods: 25 male Wistar rats with an average age of 3 weeks, and weighing 159  ±3 g were divided in seven groups (n = 5) of control (healthy), diabetes + saline, diabetes + supplement, diabetes + exercise + saline, and diabetes + supplement + exercise. To induce diabetes, streptozotocin (65 mg/kg) was injected subcutaneously, and then nicotine amid (120 mg/kg) was injected. Alpha lipoic acid was administered orally (20 mg/kg/day) for 6 weeks. The training program included intermediate interval training, including 6 weeks of training, 5 session per week, consisted of 13 periods of 4 minutes with an intensity of 70-65 percent VO2max running on a treadmill. Active rest between intervals was in the form of 2-minute runs with an intensity of 5-10 m/minute. After killing rats and sampling, pancreatic tissue was sent to the laboratory to examination the expression of VEGFR3 protein by immunohistochemistry, glucose by calorimetric method, and insulin by enzyme-linked immunoassay (ELISA)-calorimetric method. Data were analyzed using one-way ANOVA in SPSS software at a significant level of P < 0.050.Findings: 6 weeks of interval training and interval training with liposomal alpha lipoic acid had a significant effect on VEGFR3 pancreatic tissue, glucose, and serum insulin in diabetic rats. 6 weeks of liposomal alpha lipoic acid supplementation had a significant effect on VEGFR3 and serum insulin in diabetic rats.Conclusion: Intense interval training and liposomal alpha lipoic acid supplementation increased lymphangiogenesis and decreased blood glucose and favorable changes in diabetic rats.

کلیدواژه‌ها [English]

  • Diabetes Mellitus
  • Lipoic acid
  • Exercise
  • Vascular endothelial growth factor receptor-3
  • Blood glucose
  1. Yang X, Lin Y, Xu GD, Chen YS, Zhou Y, Sun J, et al. Optimal cut-off values of visceral fat area for predicting metabolic syndrome among type 2 diabetes patients in Ningbo, China. Diabetes Metab Syndr Obes 2021; 14: 1375-83.
  2. Scallan JP, Hill MA, Davis MJ. Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling. Cardiovasc Res 2015; 107(1): 89-97.
  3. Jiang X, Tian W, Nicolls MR, Rockson SG. The lymphatic system in obesity, insulin resistance, and cardiovascular diseases. Front Physiol 2019; 10: 1402.
  4. Norden PR, Kume T. The role of lymphatic vascular function in metabolic disorders. Front Physiol 2020; 11: 404.
  5. Yin N, Zhang N, Lal G, Xu J, Yan M, Ding Y, et al. Lymphangiogenesis is required for pancreatic islet inflammation and diabetes. PLoS One 2011; 6(11): e28023.
  6. 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.
  7. Shaik F, Cuthbert GA, Homer-Vanniasinkam S, Muench SP, Ponnambalam S, Harrison MA. Structural basis for vascular endothelial growth factor receptor activation and implications for disease therapy. Biomolecules 2020; 10(12): 1673.
  8. Kajiya K, Detmar M. An important role of lymphatic vessels in the control of UVB-induced edema formation and inflammation. J Invest Dermatol 2006; 126(4): 919-21.
  9. Madsen SM, Thorup AC, Overgaard K, Jeppesen PB. High intensity interval training improves glycaemic control and pancreatic beta cell function of type 2 diabetes patients. PLoS One 2015; 10(8): e0133286.
  10. Karstoft K, Winding K, Knudsen SH, James NG, Scheel MM, Olesen J, et al. 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(10): 2081-93.
  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. J Appl Physiol (1985) 2011; 111(6): 1554-60.
  12. 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. J Arak Uni Med Sci 2018; 21(6): 107-18. [In Persian].
  13. Elbadawy AM, Abd Elmoniem RO, Elsayed AM. Alpha lipoic acid and diabetes mellitus: potential effects on peripheral neuropathy and different metabolic parameters. Alexandria J Med 2021; 57(1): 113-20.
  14. Thirunavukkarasu V, Anitha Nandhini AT, Anuradha CV. Lipoic acid improves glucose utilisation and prevents protein glycation and AGE formation. Pharmazie 2005; 60(10): 772-5.
  15. 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. Physiol Int 2019; 106(3): 213-24.
  16. Dworacka M, Chukanova G, Iskakova S, Kurmambayev Y, Wesolowska 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. Eur J Pharm Sci 2018; 117: 41-7.
  17. Songstad NT, Kaspersen KH, Hafstad AD, Basnet P, Ytrehus K, Acharya G. Effects of high intensity interval training on pregnant rats, and the placenta, heart and liver of their fetuses. PLoS One 2015; 10(11): e0143095.
  18. Leandro CG, Levada AC, Hirabara SM, Manhaes-de-Castro R, De-Castro CB, Curi R, et al. A program of moderate physical training for Wistar rats based on maximal oxygen consumption. J Strength Cond Res 2007; 21(3): 751-6.
  19. Konner AC, Bruning JC. Toll-like receptors: Linking inflammation to metabolism. Trends Endocrinol Metab 2011; 22(1): 16-23.
  20. Rahbar S, Naimi SS. The effect of combined aerobic and resistance exercise on biochemical factors in patients with type 2 diabetes mellitus. J Res Rehabil Sci 2018; 14(4): 230-8. [In Persian].
  21. Oltmanns KM, Melchert UH, Scholand-Engler HG, Schultes B, Schweiger U, Peters A. Divergent effects of hyper- and hypoglycemia on circulating vascular endothelial growth factor in humans. Metabolism 2008; 57(1): 90-4.
  22. Niessen K, Zhang G, Ridgway JB, Chen H, Yan M. ALK1 signaling regulates early postnatal lymphatic vessel development. Blood 2010; 115(8): 1654-61.
  23. Solmonson A, DeBerardinis RJ. Lipoic acid metabolism and mitochondrial redox regulation. J Biol Chem 2018; 293(20): 7522-30.
  24. 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. Clin Exp Ophthalmol 2012; 40(1): e47-e57.
  25. Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A. Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes. Diabetologia 2000; 43(3): 294-303.
  26. Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, et al. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 2005; 332(3): 885-91.
  27. Juszczak F, Caron N, Mathew AV, Decleves AE. Critical role for AMPK in metabolic disease-induced chronic kidney disease. Int J Mol Sci 2020; 21(21).
  28. Ceriello A, Quagliaro L, D'Amico M, Di FC, Marfella R, Nappo F, et al. Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 2002; 51(4): 1076-82.
  29. 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. Cardiovasc Res 2014; 101(3): 364-72.
  30. Kwak SE, Lee JH, Zhang D, Song W. Angiogenesis: focusing on the effects of exercise in aging and cancer. J Exerc Nutrition Biochem 2018; 22(3): 21-6.