Effect of genistein on expression of pancreatic SIRT1, inflammatory cytokines and histological changes in ovariectomized diabetic rat | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 11، دوره 20، شماره 4، تیر 2017، صفحه 423-429 اصل مقاله (1.22 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8585 | ||
| نویسندگان | ||
| Hadi Yousefi1؛ Alireza Alihemmati2؛ Pouran Karimi3؛ Mohammad Reza Alipour1؛ Parisa Habibi1؛ Nasser Ahmadiasl* 1 | ||
| 1Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 2Department of Histology & Embryology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 3Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| چکیده | ||
| Objective(s): Genistein is reported to have anti-diabetic and anti-inflammatory functions, in particular, direct effects on β-cell proliferation and insulin secretion. In this study, we investigated the anti-inflammatory effect of genistein on the pancreatic β-cells in ovariectomized diabetic rat. Materials and Methods:Forty female rats were divided into four groups: sham, bilateral ovariectomy (OVX), OVX.D (OVX+diabetes) and OVX.D.G (OVX.D+genistein). After bilateral ovariectomy, rats in the diabetic groups were fed high-fat diet (HFD), ad libitum for 4 weeks, and then a low dose of streptozotocin (STZ) (30 mg/kg) injected intraperitoneally. Genistein (1 mg/kg/day; SC) was administrated for 8 weeks. At the end of 8 weeks, pancreas tissue was removed and used for western blotting and Hematoxylin-Eosin staining. Results: Treatment with genistein declined inflammation and tissue injury, and this decline was correlated with the expression of SIRT1. OVX and OVX.D significantly increased Nf-кB and IL-1β expression and decreased SIRT1 levels compared to sham group (P<0.05). Significant reduction of Nf-кB and IL-1β, and increasing of SIRT1 were observed during genistein treatment (P<0.05). Conclusion: Estrogen deficiency alone or with HFD increased pancreatic inflammation. However, subcutaneous administration of gtenistein prevented from these inflammatory changes in the pancreas of a surgery animal model of ovariectomy with or without diabetes. Our results support the potential preventing effect of genistein from pancreatic injury. | ||
| کلیدواژهها | ||
| Diabetes؛ Genistein؛ Inflammatory cytokines-ovariectomy؛ SIRT1 | ||
| مراجع | ||
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1. Arnush M, Heitmeier MR, Scarim AL, Marino MH, Manning PT, Corbett JA. IL-1 produced and released endogenously within human islets inhibits beta cell function. J Clin Invest 1998; 102:516.
2. Corbett JA, McDaniel ML. Intraislet release of interleukin 1 inhibits beta cell function by inducing beta cell expression of inducible nitric oxide synthase. J Exp Med 1995; 181:559-568.
3. Pfeilschifter J, Köditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr Rev 2002; 23:90-119.
4. Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nat Rev Endocrinol 2009; 5:219-226.
5. Ortis F, Miani M, Colli M, Cunha D, Gurzov E, Allagnat F, et al. Differential usage of NF-κB activating signals by IL-1β and TNF-α in pancreatic beta cells. FEBS Lett 2012; 586:984-989.
6. Lee JH, Song MY, Song EK, Kim EK, Moon WS, Han MK, et al. Overexpression of SIRT1 protects pancreatic β-cells against cytokine toxicity by suppressing the nuclear factor-κB signaling pathway. Diabetes 2009; 58:344-351.
7. Glazier MG, Bowman MA. A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy. Arch Inter Med 2001; 161:1161-1172.
8. Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function. Food Funct 2013; 4:200-212.
9. Byun EB, Sung NY, Yang MS, Lee BS, Song DS, Park JN, et al. Anti-inflammatory effect of gamma-irradiated genistein through inhibition of NF-κB and MAPK signaling pathway in lipopolysaccharide-induced macrophages. Food Chem Toxicol 2014; 74:255-264.
10. Irigoyen MC, Paulini J, Flores LJ, Flues K, Bertagnolli M, Moreira ED, et al. Exercise training improves baroreflex sensitivity associated with oxidative stress reduction in ovariectomized rats. Hypertension 2005; 46:998-1003.
11. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res 2007; 125:451.
12. Su X, Meng X, Sun C, Liu L, Su B. Intramuscular injection of soluble receptor for advanced glycation endproducts expression vector prevents the development of streptozotocin‐induced diabetes mellitus in rats on high fat diet. J Diabetes 2011; 3:309-316.
13. Habibi P, Alihemmati A, NourAzar A, Yousefi H, Mortazavi S, Ahmadiasl N. Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats. Iran J Basic Med Sci 2016; 19:381-387.
14. Dosi R, Bhatt N, Shah P, Patell R. Cardiovascular disease and menopause. J Clin Diagn Res 2014; 8:62.
15. Kim C, Edelstein SL, Crandall JP, Dabelea D, Kitabchi AE, Hamman RF, et al. Menopause and risk of diabetes in the Diabetes Prevention Program. Menopause 2011;18:857-868.
16. Choi SB, Jang JS, Park S. Estrogen and exercise may enhance β-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats. Endocrinology 2005; 146:4786-4794.
17. Donath MY, Böni-Schnetzler M, Ellingsgaard H, Ehses JA. Islet inflammation impairs the pancreatic β-cell in type 2 diabetes. Physiology 2009; 24:325-331.
18. Kim HK, Nelson-Dooley C, Della-Fera MA, Yang JY, Zhang W, Duan J, et al. Genistein decreases food intake, body weight, and fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr 2006; 136:409-414.
19. 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; 3:108-119.
20. Habibi P, Alihemmati A, Nasirzadeh M, Yousefi H, Habibi M, Ahmadiasl N. Involvement of microRNA-133 and-29 in cardiac disturbances in diabetic ovariectomized rats. Iranian J Basic Med Sci 2016; 19:1177. 21. Lee HJ, Hong YS, Yang SJ. Interaction between NLRP3 inflammasome and Sirt1/6: metabolomics approach. FASEB J 2015; 29:913.
22. Amoli MM, Larijani B. Would blockage of cytokines improve the outcome of pancreatic islet transplantation? Med Hypotheses 2006; 66:816-819.
23. Aharon-Hananel G, Jörns A, Lenzen S, Raz I, Weksler-Zangen S. Antidiabetic effect of interleukin-1β antibody therapy through β-Cell protection in the cohen diabetes-sensitive rat. Diabetes 2015; 64:1780-1785.
24. Gao X, Liu K, Huang F, Zhang D, Guo X, Wang M, et al. Positive and negative regulation of insulin action by genistein in the endothelium. J Nutr Biochem 2013; 24:222-230.
25. Hirasaka K, Maeda T, Ikeda C, Haruna M, Kohno S, Abe T, et al. Isoflavones derived from soy beans prevent MuRF1-mediated muscle atrophy in C2C12 myotubes through SIRT1 activation. J Nutr Sci Vitaminol 2013; 59:317-324.
26. Kim EK, Kwon KB, Song MY, Seo SW, Park SJ, Ka SO, et al. Genistein protects pancreatic β cells against cytokine-mediated toxicity. Mol Cell Endocrinol 2007; 278:18-28. | ||
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