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:: دوره 28، شماره 2 - ( مجله علمی دانشگاه علوم پزشکی کردستان 1402 ) ::
جلد 28 شماره 2 صفحات 11-1 برگشت به فهرست نسخه ها
بررسی اثر مهارکننده کیناز وابسته به گیرنده اینترلوکین 1 (IRAK) بر بیان ژن‌های PPAR.γ و GLUT.4 در بافت عضله موش‌های مقاوم به انسولین
بیدالله شاهوزهی1 ، سعیده معین الدینی2 ، مصطفی اللهیاری3 ، حسین فلاح 4
1- استادیار، مرکز تحقیقات فیزیولوژی، پژوهشکده علوم پایه و بالینی فیزیولوژی، دانشگاه علوم پزشکی کرمان، کرمان، ایران
2- گروه بیوشیمی بالینی، دانشکده پزشکی افضلی‌پور، دانشگاه علوم پزشکی کرمان، کرمان، ایران
3- گروه بیوشیمی، بیوفیزیک، ژنتیک و تغذیه، دانشکده پزشکی، دانشگاه علوم پزشکی گلستان، گرگان، ایران
4- دانشیار، گروه بیوشیمی بالینی، دانشکده پزشکی افضلی‌پور، دانشگاه علوم پزشکی کرمان، کرمان، ایران ، hf59ma@gmail.com
چکیده:   (1177 مشاهده)
زمینه و هدف: دیابت ملیتوس یک اختلال متابولیک با شیوع در حال افزایش در سراسر دنیا است. چاقی نقش مهمی در افزایش خطر ابتلا به دیابت، سندروم متابولیک، فشار خون و بیماری‌های قلبی عروقی دارد. التهاب خفیف ناشی از چاقی منجر به عدم تعادل در ترشح آدیپوکاین ها می‌شود و از این طریق حساسیت به انسولین را کاهش می‌دهد. خانواده TLR در این مسیرهای التهابی نقش اساسی دارند ؛ بنابراین مهار IRAK، به‌عنوان یک واسطه کلیدی این مسیر، در مهار التهاب و مقاومت انسولینی نقش دارد. به همین دلیل اثر این مهارکننده بر بیان γPPAR- و GLUT.4 را که در حساسیت انسولینی نقش دارند، بررسی کردیم.
مواد و روش‌ها: در این مطالعه از موش‌های نر نژاد C57BL/6J برای ابتلا به مقاومت انسولینی استفاده شد. موش‌ها به 6 گروه غذای استاندارد، غذای پرچرب، غذای پرچرب+حلال، غذای پرچرب+پیوگلیتازون، غذای پرچرب+مهارکننده IRAK و غذای پرچرب+ترکیب پیوگلیتازون - مهارکننده IRAK تقسیم شدند. در پایان مطالعه، موش‌ها کشته شدند و بافت عضلانی جمع‌آوری شد. بیان GLUT4 و γTPPAR- با روش Real Time PCR در بافت عضلانی اندازه‌گیری شد.
یافته‌ها: داده‌های این مطالعه نشان داد که پیوگلیتازون، مهارکننده IRAK و ترکیب IRAKi + Pioglitazone باعث افزایش بیانγ PPAR-  در بافت عضلانی می‌شود؛ ولی مهارکننده IRAK بر خلاف پیوگلیتازون اثری بر بیان GLUT.4 ندارد.
نتیجه‌گیری: نتایج این مطالعه نشان می‌دهد که احتمالاً اثرات حساس کنندگی مهارکننده IRAK به انسولین از طریق افزایش بیان PPAR-γ القا می‌شود.
واژه‌های کلیدی: دیابت ملیتوس، مقاومت به انسولین، مهارکننده IRAK، GLUT4، PPAR-γ، پیوگلیتازون
متن کامل [PDF 1696 kb]   (355 دریافت)    
نوع مطالعه: پژوهشي اصیل | موضوع مقاله: بیوشیمی و آزمایشگاه بالینی
دریافت: 1400/8/4 | پذیرش: 1400/8/30 | انتشار: 1402/3/7
فهرست منابع
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54. Yan Liang 1, Shudong Sheng, Penghua Fang, Yinping Ma, Jian Li, Qiaojia Shi, Yumei Sui MS. Exercise-induced galanin release facilitated GLUT4 translocation in adipocytes of type 2 diabetic rats. Pharmacol Biochem Behav. 2012;100(3):554-9. Available from: http://dx.doi.org/10.1016/j.pbb.2011.10.026. [DOI:10.1016/j.pbb.2011.10.026] [PMID]
55. Daugaard JR, Richter EA. Muscle- and fibre type-specific expression of glucose transporter 4, glycogen synthase and glycogen phosphorylase proteins in human skeletal muscle. Eur J Physiol. 2004;447(4):452-6. Available from: [DOI:10.1007/s00424-003-1195-8] [PMID]
56. Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications - A review. Nutr J . 2014;13(1):1-10. Available from: http://dx.doi.org/10.1186/1475-2891-13-17 [DOI:10.1186/1475-2891-13-17] [PMID] []
57. Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res. 2006;65(2):120-59. Available from: http://dx.doi.org/10.1016/j.plipres.2005.12.002 [DOI:10.1016/j.plipres.2005.12.002] [PMID]
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60. Rajaie A, Allahyari M, Nazari-Robati M, Fallah H. Inhibition of interleukin-1 receptor-associated kinases 1/4, increases gene expression and serum level of adiponectin in mouse model of insulin resistance. Int J Mol Cell Med . 2018;7(3):185-92. Available from: http://dx.doi.org/10.22088/IJMCM.BUMS.7.3.185
61. Allahyari M, Rajaie A, Fallah H. IRAK inhibitor can improve insulin sensitivity in insulin-resistant mice fed with a high-fat diet. Asian Biomed. 2020;14(6):253-60. Available from: http://dx.doi.org/10.1515/abm-2020-0034 [DOI:10.1515/abm-2020-0034] [PMID] []
62. Li Z, Younger K, Gartenhaus R, Joseph AM, Hu F, Baer MR, et al. Inhibition of IRAK1 / 4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies. J Clin Invest. 2015;125(3):1081-97. Available from: http://dx.doi.org/10.1172/JCI75821DS1 [DOI:10.1172/JCI75821DS1]
63. Yadav H, Jain S, Yadav M, Sinha PR, Prasad GBKS, Marotta F. Epigenomic derangement of hepatic glucose metabolism by feeding of high fructose diet and its prevention by Rosiglitazone in rats. Dig Liver Dis . 2009;41(7):500-8. Available from: http://dx.doi.org/10.1016/j.dld.2008.11.012 [DOI:10.1016/j.dld.2008.11.012] [PMID]
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65. Mohammadi A, Fallah H, Gholamhosseinian A. Antihyperglycemic Effect of Rosa Damascena is Mediated by PPAR.γGene Expression in Animal Model of Insulin Resistance. Iran J Pharm Res. 2017;16(3):1080-8.
66. Dabravolski SA, Orekhova VA, Baig MS, Bezsonov EE, Starodubova A V., Popkova T V., et al. The role of mitochondrial mutations and chronic inflammation in diabetes. Int J Mol Sci . 2021;22(13). Available from: http://dx.doi.org/10.3390/ijms22136733 [DOI:10.3390/ijms22136733] [PMID] []
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69. Kumar P, Kale RK, Baquer NZ. Antihyperglycemic and protective effects of Trigonella foenum graecum seed powder on biochemical alterations in alloxan diabetic rats. Eur Rev Med Pharmacol Sci. 2012;16(3):18-27.
70. Fernyhough ME, Okine E, Hausman G, Vierck JL, Dodson M V. PPARγ and GLUT-4 expression as developmental regulators/markers for preadipocyte differentiation into an adipocyte. Domest Anim Endocrinol. 2007;33(4):367-78. Available from: http://dx.doi.org/10.1016/j.domaniend.2007.05.001 [DOI:10.1016/j.domaniend.2007.05.001] [PMID]
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74. Kumar R, Balaji S, Uma TS, Sehgal PK. Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPARγ and PI3K. J Ethnopharmacol. 2009;126(3):533-7. Available from: http://dx.doi.org/10.1016/j.jep.2009.08.048. [DOI:10.1016/j.jep.2009.08.048] [PMID]
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95. Feige JN, Gelman L, Michalik L, Desvergne B, Wahli W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog Lipid Res. 2006;65(2):120-59. Available from: http://dx.doi.org/10.1016/j.plipres.2005.12.002 [DOI:10.1016/j.plipres.2005.12.002] [PMID]
96. Elstner E, Müller C, Koshizuka K, Williamson EA, Park D, Asou H, et al. Ligands for peroxisome proliferator-activated receptory and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci U S A. 1998;95(15):8806-11. Available from: http://dx.doi.org/10.1073/pnas.95.15.8806 [DOI:10.1073/pnas.95.15.8806] [PMID] []
97. Moinaldini S, Allahyari M, Shahouzehi B, Fallah H. Evaluation of the Effect of Co-administration of IRAK Inhibitor and Pioglitazone on PPAR-γ, GLUT-4, TNF-α, and Leptin Genes Expression in Adipose Tissue of Insulin-resistant Mice. J Kerman Univ Med Sci. 2021;28(2):127-38.
98. Rajaie A, Allahyari M, Nazari-Robati M, Fallah H. Inhibition of interleukin-1 receptor-associated kinases 1/4, increases gene expression and serum level of adiponectin in mouse model of insulin resistance. Int J Mol Cell Med . 2018;7(3):185-92. Available from: http://dx.doi.org/10.22088/IJMCM.BUMS.7.3.185
99. Allahyari M, Rajaie A, Fallah H. IRAK inhibitor can improve insulin sensitivity in insulin-resistant mice fed with a high-fat diet. Asian Biomed. 2020;14(6):253-60. Available from: http://dx.doi.org/10.1515/abm-2020-0034 [DOI:10.1515/abm-2020-0034] [PMID] []
100. Li Z, Younger K, Gartenhaus R, Joseph AM, Hu F, Baer MR, et al. Inhibition of IRAK1 / 4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies. J Clin Invest. 2015;125(3):1081-97. Available from: http://dx.doi.org/10.1172/JCI75821DS1 [DOI:10.1172/JCI75821DS1]
101. Yadav H, Jain S, Yadav M, Sinha PR, Prasad GBKS, Marotta F. Epigenomic derangement of hepatic glucose metabolism by feeding of high fructose diet and its prevention by Rosiglitazone in rats. Dig Liver Dis . 2009;41(7):500-8. Available from: http://dx.doi.org/10.1016/j.dld.2008.11.012 [DOI:10.1016/j.dld.2008.11.012] [PMID]
102. Fu Y, Luo N, Klein RL, Timothy Garvey W. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46(7):1369-79. Available from: http://dx.doi.org/10.1194/jlr.M400373-JLR200 [DOI:10.1194/jlr.M400373-JLR200] [PMID]
103. Mohammadi A, Fallah H, Gholamhosseinian A. Antihyperglycemic Effect of Rosa Damascena is Mediated by PPAR.γGene Expression in Animal Model of Insulin Resistance. Iran J Pharm Res. 2017;16(3):1080-8.
104. Dabravolski SA, Orekhova VA, Baig MS, Bezsonov EE, Starodubova A V., Popkova T V., et al. The role of mitochondrial mutations and chronic inflammation in diabetes. Int J Mol Sci . 2021;22(13). Available from: http://dx.doi.org/10.3390/ijms22136733 [DOI:10.3390/ijms22136733] [PMID] []
105. Ahmed I, Furlong K, Flood J, Treat VP, Goldstein BJ. Dual PPAR α/γ agonists: Promises and pitfalls in type 2 diabetes. Am J Ther. 2007;14(1):49-62. Available from: http://dx.doi.org/10.2174/138955706776876140 [DOI:10.2174/138955706776876140] [PMID]
106. Leguisamo NM, Lehnen AM, Machado UF, Okamoto MM, Markoski MM, Pinto GH, et al. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome. Cardiovasc Diabetol. 2012;11(1):1. Available from: http://dx.doi.org/10.1186/1475-2840-11-100 [DOI:10.1186/1475-2840-11-100] [PMID] []
107. Kumar P, Kale RK, Baquer NZ. Antihyperglycemic and protective effects of Trigonella foenum graecum seed powder on biochemical alterations in alloxan diabetic rats. Eur Rev Med Pharmacol Sci. 2012;16(3):18-27.
108. Fernyhough ME, Okine E, Hausman G, Vierck JL, Dodson M V. PPARγ and GLUT-4 expression as developmental regulators/markers for preadipocyte differentiation into an adipocyte. Domest Anim Endocrinol. 2007;33(4):367-78. Available from: http://dx.doi.org/10.1016/j.domaniend.2007.05.001 [DOI:10.1016/j.domaniend.2007.05.001] [PMID]
109. Elmazar MM, El-Abhar HS, Schaalan MF, Farag NA. Phytol/Phytanic Acid and Insulin Resistance: Potential Role of Phytanic Acid Proven by Docking Simulation and Modulation of Biochemical Alterations. PLoS One . 2013;8(1):1-10. Available from: [DOI:10.1371/journal.pone.0045638] [PMID] []
110. Semple RK, Chatterjee VKK, O'Rahilly S. PPARγ and human metabolic disease. J Clin Invest . 2006;116(3):581-9. Available from: http://dx.doi.org/10.1172/JCI28003 [DOI:10.1172/JCI28003] [PMID] []
111. Robbins GT, Nie D. PPARgamma, Bioactive Lipids, and Cancer Progression Gregory. Bone. 2014;23(1):1-7. Available from: http://dx.doi.org/10.2741/4021. [DOI:10.2741/4021] [PMID] []
112. Kumar R, Balaji S, Uma TS, Sehgal PK. Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPARγ and PI3K. J Ethnopharmacol. 2009;126(3):533-7. Available from: http://dx.doi.org/10.1016/j.jep.2009.08.048. [DOI:10.1016/j.jep.2009.08.048] [PMID]
113. Kim HS, Hwang YC, Koo SH, Park KS, Lee MS, Kim KW, et al. PPAR-γ Activation Increases Insulin Secretion through the Up-regulation of the Free Fatty Acid Receptor GPR40 in Pancreatic β-Cells. PLoS One. 2013;8(1):23-9. Available from: http://dx.doi.org/10.1371/journal.pone.0050128 [DOI:10.1371/journal.pone.0050128] [PMID] []
114. Collino M, Aragno M, Castiglia S, Miglio G, Tomasinelli C, Boccuzzi G, et al. Pioglitazone improves lipid and insulin levels in overweight rats on a high cholesterol and fructose diet by decreasing hepatic inflammation. Br J Pharmacol. 2010;160(8):1892-902. Available from: http://dx.doi.org/10.1111/j.1476-5381.2010.00671.x [DOI:10.1111/j.1476-5381.2010.00671.x] [PMID] []
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Shahouzehi B, Moinaldini S, Allahyari M, Fallah H. Evaluation of the effect of interleukin-1 receptor associated kinase (IRAK) inhibitor on PPAR.γ and GLUT.4 genes expression in muscle tissueof insulin resistant mice. SJKU 2023; 28 (2) :1-11
URL: http://sjku.muk.ac.ir/article-1-7043-fa.html

شاهوزهی بیدالله، معین الدینی سعیده، اللهیاری مصطفی، فلاح حسین. بررسی اثر مهارکننده کیناز وابسته به گیرنده اینترلوکین 1 (IRAK) بر بیان ژن‌های PPAR.γ و GLUT.4 در بافت عضله موش‌های مقاوم به انسولین. مجله علمي دانشگاه علوم پزشكي كردستان. 1402; 28 (2) :1-11

URL: http://sjku.muk.ac.ir/article-1-7043-fa.html



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مجله علمی دانشگاه علوم پزشکی کردستان Scientific Journal of Kurdistan University of Medical Sciences
مجله علمی دانشگاه علوم پزشکی کردستان Scientific Journal of Kurdistan University of Medical Sciences
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