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Citations93535738
h-index3827
i10-index246147

 

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Central Library of Kurdistan University of Medical Sciences
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Vice-Chancellery for Research and Technology
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:: Volume 28, Issue 2 (Scientific Journal of Kurdistan University of Medical Sciences 2023) ::
SJKU 2023, 28(2): 1-11 Back to browse issues page
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
Beydolah Shahouzehi1 , Saeedeh Moinaldini2 , Mostafa Allahyari3 , Hossein Fallah 4
1- Assistant Professor, Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
2- Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
3- Department of Biochemistry, Biophysics, Genetics and Nutrition, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
4- Associate Professor, Department of Clinical Biochemistry, Afzalipou School of Medicine, Kerman University of Medical Sciences, Kerman, Iran , hf59ma@gmail.com
Abstract:   (1153 Views)
Background and Aim: Diabetes mellitus is a metabolic disorder with an increasing prevalence in the world. Obesity plays a pivotal role in increasing the risk of diabetes, metabolic syndrome, hypertension and cardiovascular diseases. Obesity dependent mild-inflammation leads to an imbalance in the secretion of adipokines and thereby reduces insulin sensitivity. The TLR family plays an important role in these inflammatory pathways, and therefore inhibition of IRAK, as a key mediator of the pathway, plays a role in inhibiting inflammation and insulin resistance. In this study we investigated the effect of this inhibitor on the expression levels of PPAR-γ and GLUT.4, which are involved in insulin sensitivity.
Materials and Methods: In this study, male C57BL/6J mice were used for induction of insulin resistance. Mice were divided into 6 groups including standard diet, high fat diet, high fat diet + solvent, high fat diet + pioglitazone, high fat diet + IRAK inhibitor and high fat diet + combination of pioglitazone-IRAK inhibitor. At the end of the study, the mice were killed and expression levels of GLUT4 and TPPAR-γ in muscle tissue of the mice were measured by Real Time PCR.
Results: This study showed that pioglitazone, IRAK inhibitor, and the combination of IRAK inhibitor- Pioglitazone increased PPAR-γ expression in muscle tissue, but IRAK inhibitor unlike pioglitazone had no effect on GLUT.4 expression.
Conclusion: The results of this study suggested that insulin sensitizing effects of IRAK inhibitor may be induced by increasing PPAR-γ expression level.
 
Keywords: Diabetes mellitus, Insulin resistance, IRAK inhibitor, GLUT4, PPAR-γ, Pioglitazone
Full-Text [PDF 1696 kb]   (328 Downloads)    
Type of Study: Original Research | Subject: Biochemistry and Clinical Laboratory
Received: 2021/10/26 | Accepted: 2021/11/21 | Published: 2023/05/28
References
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22. 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
23. 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] []
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41. Zhao X, He Q, Zeng Y, Cheng L. Effectiveness of combined exercise in people with type 2 diabetes and concurrent overweight / obesity : a systematic review and meta-analysis. Br Med J . 2021;2021(1):1-12. Available from: http://dx.doi.org/10.1136/bmjopen-2020-046252 [DOI:10.1136/bmjopen-2020-046252] [PMID] []
42. Esteves JV, Enguita FJ, Machado UF. MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and Translocation in Insulin Resistance. J Diabetes Res. 2017;2017(1):1-11. Available from: http://dx.doi.org/10.1155/2017/7267910 [DOI:10.1155/2017/7267910] [PMID] []
43. Ou YL, Lee MY, Lin IT, Wen WL, Hsu WH, Chen SC. Obesity-related indices are associated with albuminuria and advanced kidney disease in type 2 diabetes mellitus. Ren Fail. 2021;43(1):1250-8. Available from: [DOI:10.1080/0886022X.2021.1969247] [PMID] []
44. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: A 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67(5):968-77. Available from: http://dx.doi.org/10.1161/01.CIR.67.5.968 [DOI:10.1161/01.CIR.67.5.968] [PMID]
45. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001;13(414):799-806. Available from: http://dx.doi.org/10.1038/414799a. [DOI:10.1038/414799a] [PMID]
46. Hirabara SM, Gorjão R, Vinolo MA, Rodrigues AC, Nachbar RT, Curi R. Molecular targets related to inflammation and insulin resistance and potential interventions. Vol. 2012, Journal of Biomedicine and Biotechnology. 2012. p. 1-16. Available from: http://dx.doi.org/10.1155/2012/379024 [DOI:10.1155/2012/379024] [PMID] []
47. Han SH, Sakuma I, Shin EK, Koh KK. Antiatherosclerotic and Anti-Insulin Resistance Effects of Adiponectin: Basic and Clinical Studies. Prog Cardiovasc Dis. 2009;52(2):126-40. Available from: http://dx.doi.org/10.1016/j.pcad.2009.06.004. [DOI:10.1016/j.pcad.2009.06.004] [PMID]
48. Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes . 2011 Apr;18(2):139-43. Available from: http://dx.doi.org/10.1097/MED.0b013e3283444b09 [DOI:10.1097/MED.0b013e3283444b09] [PMID] []
49. Kawai T, Akira S. TLR signaling. Cell Death Differ. 2006;13(5):816-25. Available from: http://dx.doi.org/10.1186/1475-2891-13-17 [DOI:10.1186/1475-2891-13-17] [PMID] []
50. Wang Z, Wesche H, Stevens T, Walker N, Yeh W-C. IRAK-4 Inhibitors for Inflammation. Curr Top Med Chem . 2009;9(8):724-37. Available from: http://dx.doi.org/10.2174/156802609789044407 [DOI:10.2174/156802609789044407] [PMID] []
51. Chiu L-L, Chou S-W, Cho Y-M, Ho H-Y, Ivy JL, Hunt D, et al. Effect of prolonged intermittent hypoxia and exercise training on glucose tolerance and muscle GLUT4 protein expression in rats. J Biomed Sci [Internet]. 2004;11(6):838-46. Available from: 10.1007/BF02254369 [DOI:10.1007/BF02254369] [PMID]
52. Huang S, Czech MP. The GLUT4 Glucose Transporter. Cell Metab. 2007;5(4):237-52. Available from: [DOI:10.1016/j.cmet.2007.03.006] [PMID]
53. Li W, Dai R-J, Yu Y-H, Li L, Wu C-M, Luan W-W, et al. Antihyperglycemic effect of Cephalotaxus sinensis leaves and GLUT-4 translocation facilitating activity of its Flavonoid constituents. Biol Pharm Bull. 2007;30(6):1123-9. Available from: http://dx.doi.org/10.1248/bpb.30.1123. [DOI:10.1248/bpb.30.1123] [PMID]
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]
58. 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] []
59. 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.
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]
64. 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]
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] []
67. 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]
68. 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] []
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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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
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Volume 28, Issue 2 (Scientific Journal of Kurdistan University of Medical Sciences 2023) Back to browse issues page
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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