Swimming Impacts on Pancreatic Inflammatory Cytokines, miR-146a and NF-кB Expression Levels in Type-2 Diabetic Rats

Author(s): Mohammad Reza Alipour, Nasibeh Yousefzade, Fariba Mirzaei Bavil, Roya Naderi, Rafighe Ghiasi*

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 8 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background: Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and type-2 diabetes.

Objective: This study aimed to evaluate the effect of swimming exercise on pancreatic expression levels of inflammatory cytokines, miR-146a and NF-кB in type-2 diabetic male rats.

Methods: Twenty- eight male Wistar rats were divided into four groups: control (Con), exercise, diabetes and diabetic exercise (n = 7). Diabetes induction performed by the combination of high-fat diet (HFD, 4 weeks) and streptozotocin (35 mg/kg. ip). After induction of diabetes, the rats swam in the exercise groups for 12 weeks. Then, blood and tissue samples were collected.

Results: Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group.

Conclusion: Our results indicated a significant increase in expression levels of miR-146, NF-κB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-кB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group.

Keywords: Diabetes, inflammatory cytokines, NF-кB, miR-146a, IRAK1, TRAF6.

[1]
American Diabetes Association; 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018. Diabetes care 2018.1; 41(Supplement ): S13-27..
[2]
Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007.1; 56(7): 1761- 72..
[http://dx.doi.org/10.2337/db06-1491]
[3]
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444(7121): 840-6.
[http://dx.doi.org/10.1038/nature05482] [PMID: 17167471]
[4]
Ghiasi R, Ghadiri Soufi F, Somi MH, et al. hossein Somi M, Mohaddes G, Bavil FM, Naderi R, Alipour MR. Swim training improves HOMA-IR in type 2 diabetes induced by high fat diet and low dose of streptozotocin in male rats. Adv Pharm Bull 2015; 5(3): 379-84.
[http://dx.doi.org/10.15171/apb.2015.052] [PMID: 26504760]
[5]
Malik VS, Popkin BM, Bray GA, Després JP, Hu FB. Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation 2010; 121(11): 1356-64.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.876185] [PMID: 20308626]
[6]
Friedrich N. Metabolomics in diabetes research. J Endocrinol 2012; 215(1): 29-42.
[http://dx.doi.org/10.1530/JOE-12-0120] [PMID: 22718433]
[7]
Bastard JP, Maachi M, Lagathu C, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. European cytokine network 2006. 1; 17(1): 4-12..
[8]
Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. he Journal of clinical investigation 2003. 15; 112(12): 1821-30..
[http://dx.doi.org/10.1172/JCI200319451]
[9]
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. Creactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus Jama 2001.18;286(3): 327-4..
[10]
Vachharajani V, Granger DN. Adipose tissue: a motor for the inflammation associated with obesity. IUBMB Life 2009; 61(4): 424-30.
[http://dx.doi.org/10.1002/iub.169] [PMID: 19319966]
[11]
Oliver E, McGillicuddy F, Phillips C, Toomey S, Roche HM. The role of inflammation and macrophage accumulation in the development of obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chain n-3 PUFA. Proc Nutr Soc 2010; 69(2): 232-43.
[http://dx.doi.org/10.1017/S0029665110000042] [PMID: 20158940]
[12]
Arkan MC, Hevener AL, Greten FR, et al. IKK-β links inflammation to obesity-induced insulin resistance. Nat Med 2005; 11(2): 191-8.
[http://dx.doi.org/10.1038/nm1185] [PMID: 15685170]
[13]
Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. Diabetes mellitus, a microRNA-related disease?. Translational Research 2011. 1;157(4): 253-64..
[14]
He A, Zhu L, Gupta N, Chang Y, Fang F. Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Molecular endocrinology 1;21(11): 2785-94.. 2007.
[15]
Chakraborty C, Doss CG, Bandyopadhyay S, Agoramoorthy G. Influence of miRNA in insulin signaling pathway and insulin resistance: micro-molecules with a major role in type-2 diabetes. Wiley Interdiscip Rev RNA 2014; 5(5): 697-712.
[http://dx.doi.org/10.1002/wrna.1240] [PMID: 24944010]
[16]
Roggli E, Britan A, Gattesco S, et al. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic β-cells. Diabetes 2010. 1; 59(4): 978-86..
[http://dx.doi.org/10.2337/db09-0881]
[17]
Williams AE, Perry MM, Moschos SA, Larner-Svensson HM, Lindsay MA. Role of miRNA-146a in the regulation of the innate immune response and cancer. 2008.36: 1211-5..
[http://dx.doi.org/10.1042/BST0361211]
[18]
Baldeón L, Weigelt K, de Wit H, et al. Type 2 diabetes monocyte microRNA and mRNA expression: dyslipidemia associates with increased differentiation-related genes but not inflammatory activation. Plos One 2015.7;10(6):. e0129421
[http://dx.doi.org/10.1371/journal.pone.0129421]
[19]
Kamali K, Korjan ES, Eftekhar E, Malekzadeh K, Soufi FG. The role of miR-146a on NF-κB expression level in human umbilical vein endothelial cells under hyperglycemic condition. Bratisl Lek Listy 2016; 117(7): 376-80.
[http://dx.doi.org/10.4149/BLL_2016_074] [PMID: 27546538]
[20]
Rojas J, Bermudez V, Palmar J, et al. Pancreatic beta cell death: novel potential mechanisms in diabetes therapy. J Diabet Res 2018; 2018.
[http://dx.doi.org/10.1155/2018/9601801]
[21]
Zilahi E, Tarr T, Papp G, Griger Z, Sipka S, Zeher M. Increased microRNA-146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren's syndrome immunology letters 2012. 30;141(2): 165-8..
[22]
Feng J, Xing W, Xie L. Regulatory roles of microRNAs in diabetes. Int J Mol Sci 2016; 17(10): 1729.
[http://dx.doi.org/10.3390/ijms17101729] [PMID: 27763497]
[23]
Kivelä R, Silvennoinen M, Touvra AM, et al. Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle. FASEB J 2006; 20(9): 1570-2.
[http://dx.doi.org/10.1096/fj.05-4780fje] [PMID: 16816123]
[24]
Teixeira de Lemos E, Pinto R, Oliveira J, et al. Differential effects of acute (extenuating) and chronic (training) exercise on inflammation and oxidative stress status in an animal model of type 2 diabetes mellitus Mediators of inflammation 2011; 2011
[25]
de Lemos ET, Reis F, Baptista S, et al. Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats Nutrition 2009. 1; 25(3): 330-9..
[26]
Habibi F, Ghadiri Soufi F, Ghiasi R, Khamaneh AM, Alipour MR. Alteration in inflammation-related miR-146a expression in NF-KB signaling pathway in diabetic rat hippocampus. Adv Pharm Bull 2016; 6(1): 99-103.
[http://dx.doi.org/10.15171/apb.2016.015] [PMID: 27123424]
[27]
Li L, Chen XP, Li YJ. MicroRNA-146a and human disease. Scand J Immunol 2010; 71(4): 227-31.
[http://dx.doi.org/10.1111/j.1365-3083.2010.02383.x] [PMID: 20384865]
[28]
Lovis P, Roggli E, Laybutt DR, et al. Alterations in microRNA expression contribute to fatty acid–induced pancreatic β-cell dysfunction. Journal of applied physiology 2008. 1;57(10): 2728-36..
[http://dx.doi.org/10.2337/db07-1252]
[29]
Balasubramanyam M, Aravind S, Gokulakrishnan K, et al. Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes. Molecular and cellular biochemistry 2011.1; 351(1-2): 197-205..
[http://dx.doi.org/10.1007/s11010-011-0727-3]
[30]
Oghbaei H, Ahmadi Asl N, Sheikhzadeh F, Alipour MR, Khamaneh AM. The effect of regular moderate exercise on miRNA-192 expression changes in kidney of streptozotocin-induced diabetic male rats. Adv Pharm Bull 2015; 5(1): 127-32.
[PMID: 25789230]
[31]
Kangas R, Laakkonen E. Physical activity responsive miRNAs-Potential mediators of training responses in human skeletal muscle? J Sport Health Sci 2013; 2.
[http://dx.doi.org/10.1016/j.jshs.2013.04.002]
[32]
Sawada S, Kon M, Wada S, Ushida T, Suzuki K, Akimoto T. Profiling of circulating microRNAs after a bout of acute resistance exercise in humans. PloS one 2013. 29; 8(7):. e70823
[http://dx.doi.org/10.1371/journal.pone.0070823]
[33]
Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-kappaB. Nat Med 2005; 11(2): 183-90.
[http://dx.doi.org/10.1038/nm1166] [PMID: 15685173]
[34]
Shurtz-Swirski R, Sela S, Herskovits AT, et al. Involvement of peripheral polymorphonuclear leukocytes in oxidative stress and inflammation in type 2 diabetic patients. Diabetes care 1;24(1): 104-.2001;.
[http://dx.doi.org/10.2337/diacare.24.1.104]
[35]
Ho E, Bray TM. Antioxidants, NFkappaB activation, and diabetogenesis. Proc Soc Exp Biol Med 1999; 222(3): 205-13.
[http://dx.doi.org/10.1046/j.1525-1373.1999.d01-137.x] [PMID: 10601879]
[36]
Buford TW, Cooke MB, Willoughby DS. Resistance exercise-induced changes of inflammatory gene expression within human skeletal muscle. European journal of applied physiology 2009.1;107(4): 463.
[http://dx.doi.org/10.1007/s00421-009-1145-z]
[37]
Puppa MJ, White JP, Velázquez KT, et al. The effect of exercise on IL-6-induced cachexia in the Apc Min/+ mouse Journal of cachexia, sarcopenia and muscle 2012.1;3(2): 117-37..
[38]
Kramer HF, Goodyear LJ. Exercise, MAPK, and NF-kappaB signaling in skeletal muscle. J Appl Physiol 2007; 103(1): 388-95.
[http://dx.doi.org/10.1152/japplphysiol.00085.2007] [PMID: 17303713]
[39]
Vider J, Laaksonen DE, Kilk A, et al. Physical exercise induces activation of NF-kappaB in human peripheral blood lymphocytes. Antioxid Redox Signal 2001; 3(6): 1131-7.
[http://dx.doi.org/10.1089/152308601317203639] [PMID: 11813986]
[40]
Durham WJ, Li YP, Gerken E, et al. Fatiguing exercise reduces DNA binding activity of NF-kappaB in skeletal muscle nuclei. J Appl Physiol 2004; 97(5): 1740-5.
[http://dx.doi.org/10.1152/japplphysiol.00088.2004] [PMID: 15208298]
[41]
Hak AE, Pols HA, Stehouwer CD, et al. Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study. The Journal of Clinical Endocrinology & Metabolism 2001.1;86(9): 4398-05..
[http://dx.doi.org/10.1210/jcem.86.9.7873]
[42]
Tuttle HA, Davis-Gorman G, Goldman S, Copeland JG, McDonagh PF. Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease. Journal of Diabetes and its Complications 2004.1;18(6): 343-51..
[http://dx.doi.org/10.1016/S1056-8727(03)00088-6]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 8
Year: 2020
Page: [889 - 894]
Pages: 6
DOI: 10.2174/1573399815666191115154421
Price: $65

Article Metrics

PDF: 16
HTML: 1