Sirtuin1 is a regulator of oxidative stress involved in the management of diabetes complications. Due to the beneficial effects of swimming training in diabetes, this study aimed to investigate the effects of swimming training on pancreatic Sirtuin1, oxidative stress and metabolic parameters in type 2 diabetic male rats.
Materials and methods
Twenty-eight male Wistar rats (200–250 g) were randomly divided into four groups: control, diabetic, swim trained and swim trained diabetic rats (n = 7). Diabetes was induced by a high-fat diet and streptozotocin injection [35/kg intraperitoneally]. After 72 hours, animals with blood glucose levels ≥300 mg/dL were considered diabetic. Seven days after the induction of diabetes, animals in the exercise groups were subjected to swimming training (60 min/daily, 5 days/week) for 12 weeks. At the end of the intervention, the animals were anesthetized, and tissue/blood samples were prepared for measurements of metabolic parameters, albumin, the Sitruin1 gene and its protein expression levels, oxidative stress and histological study.
This study indicated that the diabetic rats had a significant decrease (p < 0.01, p < 0.05) in pancreatic Sitruin1 gene and its protein expression levels, antioxidant enzymes, serum albumin, and the quantitative insulin sensitivity check index, but a significant increase (p < 0.01) in malondialdehyde level. Swimming training resulted in a considerable improvement (p < 0.01, p < 0.05) in pancreatic Sitruin1 gene and its protein expression levels, antioxidant enzymes, serum levels of albumin and metabolic parameters. In addition, histological findings indicated the beta-cells conservation.
This study suggested that pancreatic Sitruin1 may be a promising therapeutic target for diabetic complications.
Funding source: Liver and Gastrointestinal Diseases Research Center of Tabriz University of Medical Sciences
Award Identifier / Grant number: 5/4/610
Funding statement: This study was financially supported by Liver and Gastrointestinal Diseases Research Center of Tabriz University of Medical Sciences (Project No: 5/4/610).
Author contributions: All authors have contributed in different parts of the study.
Conflict of interest: None.
Informed consent: Not applicable.
Ethical approval: This study was designed based on the protocol in accordance with the National Institutes of Health (NIH) Guide, for laboratory animal’s care.
 American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes – 2018. Diabetes Care. 2018;41(Suppl 1):S13–27.29222373 Search in Google Scholar
 Ceolotto G, Gallo A, Miola M, Sartori M, Trevisan R, Del Prato S, et al. Protein kinase C activity is acutely regulated by plasma glucose concentration in human monocytes in vivo. Diabetes. 1999;48:1316–22.10.2337/diabetes.48.6.131610342822 Search in Google Scholar
 Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Proinflammatory effects of glucose and anti-inflammatory effect of insulin: relevance to cardiovascular disease. Am J Cardiol. 2007;99:15–26.10.1016/j.amjcard.2006.11.003 Search in Google Scholar
 Igarashi M, Wakasaki H, Takahara N, Ishii H, Jiang Z-Y, Yamauchi T, et al. Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J Clin Invest. 1999;103:185–95.10.1172/JCI33269916130 Search in Google Scholar
 Jain SK, Kannan K, Lim G, Matthews-Greer J, McVie R, Bocchini JA. Elevated blood interleukin-6 levels in hyperketonemic type 1 diabetic patients and secretion by acetoacetate-treated cultured U937 monocytes. Diabetes Care. 2003;26:2139–43.10.2337/diacare.26.7.213912832326 Search in Google Scholar
 Shanmugam N, Reddy MA, Guha M, Natarajan R. High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells. Diabetes. 2003;52:1256–64.1271676110.2337/diabetes.52.5.1256 Search in Google Scholar
 Henriksen EJ, Diamond-Stanic MK, Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2011;51:993–9.2116334710.1016/j.freeradbiomed.2010.12.005 Search in Google Scholar
 Yun J-M, Chien A, Jialal I, Devaraj S. Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights. J Nutr Biochem. 2012;23:699–705.2181327110.1016/j.jnutbio.2011.03.012 Search in Google Scholar
 Wang YQ, Cao Q, Wang F, Huang LY, Sang TT, Liu F, et al. SIRT1 protects against oxidative stress-induced endothelial progenitor cells apoptosis by inhibiting FOXO3a via FOXO3a ubiquitination and degradation. J Cell Physiol. 2015;230:2098–107.10.1002/jcp.2493825640014 Search in Google Scholar
 Hida Y, Kubo Y, Murao K, Arase S. Strong expression of a longevity-related protein, SIRT1, in Bowen’s disease. Arch Dermatol Res. 2007;299:103–6.1718065610.1007/s00403-006-0725-6 Search in Google Scholar
 Ota H, Eto M, Ogawa S, Iijima K, Akishita M, Ouchi Y, et al. SIRT1/eNOS axis as a potential target against vascular senescence, dysfunction and atherosclerosis. J Atheroscler Thromb. 2010;17:431–5.2021570810.5551/jat.3525 Search in Google Scholar
 Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450:712–6.1804640910.1038/nature06261 Search in Google Scholar
 Gurd B. Deacetylation of PGC-1α by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis. Appl Physiol Nutr Metab. 2011;36:589–97.10.1139/h11-07021888529 Search in Google Scholar
 Wu L, Zhou L, Lu Y, Zhang J, Jian F, Liu Y, et al. Activation of SIRT1 protects pancreatic β-cells against palmitate-induced dysfunction. Biochim Biophys Acta Mol Basis Dis. 2012;1822:1815–25.10.1016/j.bbadis.2012.08.009 Search in Google Scholar
 Yu J, Zheng J, Liu X, Feng Z, Zhang X, Cao L. Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression. Braz J Med Biol Res. 2016;49.e5129.27143172 Search in Google Scholar
 Ghiasi R, Soufi FG, Hossein Somi M, Mohaddes G, Bavil FM, Naderi R, 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;5:379–84.2650476010.15171/apb.2015.052 Search in Google Scholar
 Srinivasan K, Viswanad B, Asrat L, Kaul C, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005;52:313–20.10.1016/j.phrs.2005.05.004 Search in Google Scholar
 Ghiasi R, Ghadiri FS, Mohaddes G, Alihemmati A, Somi MH, Ebrahimi H, et al. Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats. Gen Physiol Biophys. 2016;35:469–76.10.4149/gpb_201600727608615 Search in Google Scholar
 Carrillo M-C, Kanai S, Nokubo M, Kitani K. (−) Deprenyl induces activities of both superoxide dismutase and catalase but not of glutathione peroxidase in the striatum of young male rats. Life Sci. 1991;48:517–21.10.1016/0024-3205(91)90466-O1899460 Search in Google Scholar
 Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.10.1210/jcem.85.7.666110902785 Search in Google Scholar
 Lowry OH. Rosebrough, NJ, Farr, AL, Randall, RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–75. Search in Google Scholar
 Majd NE, Tabandeh MR, Shahriari A, Soleimani ZJ. Okra (Abelmoscus esculentus) improved islets structure, and down-regulated PPARs gene expression in pancreas of high-fat diet and streptozotocin-induced diabetic rats. Cell J. 2018;20:31–40.29308616 Search in Google Scholar
 Bavil FM, Alipour MR, Keyhanmanesh R, Alihemmati A, Ghiyasi R, Mohaddes G. Ghrelin decreases angiogenesis, HIF-1α and VEGF protein levels in chronic hypoxia in lung tissue of male rats. Adv Pharm Bull. 2015;5:315–20.10.15171/apb.2015.04426504752 Search in Google Scholar
 Yu W, Wan Z, Qiu X-F, Chen Y, Dai Y-T. Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats. Asian J Androl. 2013;15:646–51.2379233910.1038/aja.2013.60 Search in Google Scholar
 Luu L, Dai F, Prentice K, Huang X, Hardy A, Hansen JB, et al. The loss of Sirt1 in mouse pancreatic beta cells impairs insulin secretion by disrupting glucose sensing. J Diabetologia. 2013;56:2010–20.10.1007/s00125-013-2946-5 Search in Google Scholar
 Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschöp MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci USA. 2008;105:9793–8.10.1073/pnas.0802917105 Search in Google Scholar
 Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Babendure JL, et al. SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Mol Cell Biol. 2009;29:1363–74.1910374710.1128/MCB.00705-08 Search in Google Scholar
 Ferrara N, Rinaldi B, Corbi G, Conti V, Stiuso P, Boccuti S, et al. Exercise training promotes SIRT1 activity in aged rats. Rejuvenat Res. 2008;11:139–50.10.1089/rej.2007.0576 Search in Google Scholar
 de Ligt M, Timmers S, Schrauwen P. Resveratrol and obesity: can resveratrol relieve metabolic disturbances? Biochim Biophys Acta Mol Basis Dis. 2015;1852:1137–44.10.1016/j.bbadis.2014.11.012 Search in Google Scholar
 Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, et al. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab. 2007;6:307–19.1790855910.1016/j.cmet.2007.08.014 Search in Google Scholar
 Kitada M, Kume S, Kanasaki K, Takeda-Watanabe A, Koya D. Sirtuins as possible drug targets in type 2 diabetes. Curr Drug Targets. 2013;14:622–36.2344554310.2174/1389450111314060002 Search in Google Scholar
 Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells. PLoS Biol. 2005;4:e31.16366736 Search in Google Scholar
 Ramsey KM, Mills KF, Satoh A, SI I. Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell. 2008;7:78–88.1800524910.1111/j.1474-9726.2007.00355.x Search in Google Scholar
 Khowailed EA, Seddiek HA, Mahmoud MM, Rashed LA, Ibrahim FE. Effect of metformin on Sirtuin-1 disorders associated with diabetes in male rats. Alexandria J Med. 2018;54:373–81.10.1016/j.ajme.2017.09.002 Search in Google Scholar
 Santos L, Escande C, Denicola A. Potential modulation of sirtuins by oxidative stress. Oxid Med Cell Longev. 2016;2016:1–12. Search in Google Scholar
 Ding M, Lei J, Han H, Li W, Qu Y, Fu E, et al. SIRT1 protects against myocardial ischemia-reperfusion injury via activating eNOS in diabetic rats. Cardiovasc Diabetol. 2015;14:143.10.1186/s12933-015-0299-826489513 Search in Google Scholar
 Kitada M, Kume S, Imaizumi N, Koya D. Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1-independent pathway. Diabetes. 2011;60:634–43.2127027310.2337/db10-0386 Search in Google Scholar
 Rojas J, Bermudez V, Palmar J, Martínez MS, Olivar LC, Nava M, et al. Pancreatic beta cell death: novel potential mechanisms in diabetes therapy. J Diabetes Res. 2018;2018. Article ID: 9601801.29670917 Search in Google Scholar
 Higashida K, Kim SH, Jung SR, Asaka M, Holloszy JO, Han D-H. Effects of resveratrol and SIRT1 on PGC-1α activity and mitochondrial biogenesis: a reevaluation. PLoS Biol. 2013;11:e1001603.23874150 Search in Google Scholar
 Hori YS, Kuno A, Hosoda R, Horio Y. Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress. PLoS One. 2013;8:e73875.24040102 Search in Google Scholar
 Suwa M, Nakano H, Radak Z, Kumagai S. Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α protein expressions in rat skeletal muscle. J Metab. 2008;57:986–98.10.1016/j.metabol.2008.02.017 Search in Google Scholar
 Chong ZZ, Shang YC, Wang S, Maiese K. SIRT1: new avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets. 2012;16:167–78.10.1517/14728222.2012.64892622233091 Search in Google Scholar
 Corbi G, Conti V, Scapagnini G, Filippelli A, Ferrara N. Role of sirtuins, calorie restriction and physical activity in aging. Front Biosci (Elite Ed). 2012;4:768–78.22201912 Search in Google Scholar
 Sitar ME, Aydin S, Cakatay U. Human serum albumin and its relation with oxidative stress. J Clean Lab. 2013;59:945–52. Search in Google Scholar
 Ghiasi R, Mohammadi M, Helan JA, Jozani SR, Mohammadi S, Ghiasi A, et al. Influence of two various durations of resistance exercise on oxidative stress in the male rat’s hearts. J Cardiovascul. 2015;7:149–153. Search in Google Scholar
 Vezzoli A, Pugliese L, Marzorati M, Serpiello FR, La Torre A, Porcelli S. Time-course changes of oxidative stress response to high-intensity discontinuous training versus moderate-intensity continuous training in masters runners. PLoS One. 2014;9:e87506.24498121 Search in Google Scholar
 El-Kordy EA, Alshahrani AM. Effect of genistein, a natural soy isoflavone, on pancreatic β-cells of streptozotocin-induced diabetic rats: histological and immunohistochemical study. J Microsc Ultrastruct. 2015;3:108–19.10.1016/j.jmau.2015.03.00530023190 Search in Google Scholar
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