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Ghowsi, Mahnaz, Sisakhtnezhad, Sajjad. (1400). Down-regulation of insulin substrate receptor 1 and 2 in the liver may be a mechanism for insulin resistance during testosterone deprivation. , 9(1), 23-40. doi: 10.22070/jbcp.2021.14471.1142
Mahnaz Ghowsi; Sajjad Sisakhtnezhad. "Down-regulation of insulin substrate receptor 1 and 2 in the liver may be a mechanism for insulin resistance during testosterone deprivation". , 9, 1, 1400, 23-40. doi: 10.22070/jbcp.2021.14471.1142
Ghowsi, Mahnaz, Sisakhtnezhad, Sajjad. (1400). 'Down-regulation of insulin substrate receptor 1 and 2 in the liver may be a mechanism for insulin resistance during testosterone deprivation', , 9(1), pp. 23-40. doi: 10.22070/jbcp.2021.14471.1142
Ghowsi, Mahnaz, Sisakhtnezhad, Sajjad. Down-regulation of insulin substrate receptor 1 and 2 in the liver may be a mechanism for insulin resistance during testosterone deprivation. , 1400; 9(1): 23-40. doi: 10.22070/jbcp.2021.14471.1142

Down-regulation of insulin substrate receptor 1 and 2 in the liver may be a mechanism for insulin resistance during testosterone deprivation

Journal of Basic and Clinical Pathophysiology
مقاله 4، دوره 9، شماره 1، مرداد 2021، صفحه 23-40    اصل مقاله (720.85 K)
نوع مقاله: Research Paper
شناسه دیجیتال (DOI): 10.22070/jbcp.2021.14471.1142
نویسندگان
Mahnaz Ghowsi* ؛ Sajjad Sisakhtnezhad
Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran
چکیده
Background and Objective: Type 2 diabetes is a global concern worldwide. Despite extensive studies on the physiological effects of diabetes on the testicular functions, the impact of testosterone deficiency on the glucose homeostasis remains to be clarified. This study was designed to investigate the effects of testosterone deprivation and its replacement with testosterone enanthate on the molecular mechanisms of insulin signaling pathway in the liver of rats.
Materials and Methods: We first established a rat model of testosterone deficiency by castration (CAS-S). Subsequently, the castrated rats were administrated by subcutaneous injection of testosterone (CAS-T). Thereafter, fasting blood glucose (FBG), insulin, and homeostasis model-insulin resistance (HOMA-IR) level was assessed. The testosterone and insulin levels were further analyzed by ELISA. The mRNA expression of insulin receptor (IR)-β, insulin receptor-substrate (IRS)1 and 2 as well as glucose transporter (GLUT) 2 in the liver was analyzed by q-RT-PCR assay.
Results: Our data showed that testosterone deprivation significantly increases FBG and HOMA-IR and down-regulates IRS-1 and IRS-2 mRNA expression in the liver. However, the mRNA expression of GLUT2 and IR-β was not affected. We also found that testosterone administration could improve the liver insulin resistance.
Conclusion: These findings suggested that testosterone deprivation can impact insulin signaling in the liver via suppressing expression of IRS-1 and IRS-2 mRNA and treatment with testosterone can improve the insulin resistance in the castrated rats. Further experimental and clinical pathways are needed to be assessed for clinical application of our finding.
کلیدواژه‌ها
Androgen؛ Hepatic insulin resistance؛ Diabetes؛ IRS 1 and 2؛ Glucose transporter 2
مراجع
  1. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes–global burden of disease and forecasted trends. Journal of Epidemiology and Global Health 2020; 10(1):107-111. doi: 10.2991/jegh.k.191028.001.
  2. Xu W, Morford J, Mauvais-Jarvis F. Emerging role of testosterone in pancreatic β cell function and insulin secretion. Journal of Endocrinology 2019;240(3):R97-R105.
  3. Inaba M, Otani Y, Nishimura K, Takaha N, Okuyama A, Koga M, et al. Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. Metabolism 2005; 54(1):55-9. doi: 10.1016/j.metabol.2004.07.010.
  4. Keating NL, O'Malley AJ, Freedland SJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. Journal of the National Cancer Institute 2010; 102(1):39-46. doi: 10.1093/jnci/djp404.
  5. Cheruiyot I, Olabu B, Kamau M, Ongeti K, Mandela P. Histomorphological changes in the common carotid artery of the male rat in induced hypogonadism. Anatomy & Cell Biology 2018; 51(4):284-291. doi: 10.5115/acb.2018.51.4.284
  6. Liao N, Zheng Y, Xie H, Zhao B, Zeng Y, Liu X, et al. Adipose tissue-derived stem cells ameliorate hyperglycemia, insulin resistance and liver fibrosis in the type 2 diabetic rats. Stem Cell Research & Therapy 2017; 8(1):286. doi: 10.1186/s13287-017-0743-7.
  7. Kubota N, Kubota T, Kajiwara E, Iwamura T, Kumagai H, Watanabe T, et al. Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity. Nature Communications 2016; 7:12977. doi: 10.1038/ncomms12977.
  8. Xing L-J, Zhang L, Liu T, Hua Y-Q, Zheng P-Y, Ji G. Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease (NAFLD) rat liver. European Journal of Pharmacology 2011; 668(3):467-71. doi: 10.1016/j.ejphar.2011.07.036.
  9. Previs SF, Withers DJ, Ren J-M, White MF, Shulman GI. Contrasting effects of IRS-1 versus IRS-2 gene disruption on carbohydrate and lipid metabolism in vivo. Journal of Biological Chemistry 2000; 275(50):38990-4. doi: 10.1074/jbc.M006490200.
  10. Kiani F, Sayehmiri F, Hasanpour Dehkordi A, Motedayen M. Surveying the relationship between Gly1057Asp polymorphism of IRS-2 gene and susceptibility to type 2 diabetes; a systematic review and meta-analysis study. Journal of Renal Injury Prevention 2019;8(4) 263-270. doi: 10.15171/jrip.2019.50
  11. Schattner A, Katz-Porat B-S, Gindin Y, Geltner D. Cyproterone-induced hyperosmolar hyperglycemia. Drug Intelligence & Clinical Pharmacy 1988; 22(7-8):632-3. doi: 10.1177/106002808802200728
  12. Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care 2011; 34(4):828-37. doi: 10.2337/dc10-1233
  13. Grossmann M, Hoermann R, Wittert G, Yeap BB. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta‐analysis of randomized controlled clinical trials. Clinical Endocrinology 2015; 83(3):344-51. doi: 10.1111/cen.12664.
  14. Xia F, Xu X, Zhai H, Meng Y, Zhang H, Du S, et al. Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats. Reproductive Biology and Endocrinology 2013; 11:106. doi: 10.1186/1477-7827-11-106
  15. Chin K-Y, Ima-Nirwana S. The effects of testosterone deficiency and its replacement on inflammatory markers in rats: a pilot study. International Journal of Endocrinology and Metabolism 2017;15(1)e43053. doi: 10.5812/ijem.43053
  16. 16.               Aref A-BM, Ahmed OM, Ali LA, Semmler M. Maternal rat diabetes mellitus deleteriously affects insulin sensitivity and Beta-cell function in the offspring. Journal of diabetes Research 2013:429154. doi: 10.1155/2013/429154.
  17. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nature Protocols 2008; 3(6):1101-8. doi: 10.1038/nprot.2008.73.
  18. Vanderschueren D, Jans I, Van Herck E, Moermans K, Verhaeghe J, Bouillon R. Time-related increase of biochemical markers of bone turnover in androgen-deficient male rats. Bone and Mineral 1994; 26(2):123-31. doi: 10.1016/s0169-6009(08)80057-8.
  19. Christoffersen B, Raun K, Svendsen O, Fledelius C, Golozoubova V. Evalution of the castrated male Sprague–Dawley rat as a model of the metabolic syndrome and type 2 diabetes. International Journal of Obesity 2006; 30(8):1288-97. doi: 10.1038/sj.ijo.0803261.
  20. Dimitriadis GK, Randeva HS, Aftab S, Ali A, Hattersley JG, Pandey S, et al. Metabolic phenotype of male obesity-related secondary hypogonadism pre-replacement and post-replacement therapy with intra-muscular testosterone undecanoate therapy. Endocrine 2018; 60(1):175-184. doi: 10.1007/s12020-017-1516-x.
  21. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, Magnuson MA, et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Molecular Cell 2000;6(1):87-97. PMID: 10949030
  22. Kawaguchi T, Taniguchi E, Itou M, Sakata M, Sumie S, Sata M. Insulin resistance and chronic liver disease. World Journal of Hepatology 2011; 3(5):99-107. doi: 10.4254/wjh.v3.i5.99.
  23. Xie Z, Hao H, Tong C, Cheng Y, Liu J, Pang Y, et al. Human umbilical cord‐derived mesenchymal stem cells elicit macrophages into an anti‐inflammatory phenotype to alleviate insulin resistance in type 2 diabetic rats. Stem cells 2016; 34(3):627-39. doi: 10.1002/stem.2238.
  24. Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014; 510(7503):84-91. doi: 10.1038/nature13478.
  25. Baranova A, Tran T, Birerdinc A, Younossi Z. Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non‐alcoholic fatty liver disease. Alimentary Pharmacology & Therapeutics 2011;33(7):801-14. doi: 10.1111/j.1365-2036.2011.04579.x.
  26. Zhang J, Ou J, Bashmakov Y, Horton JD, Brown MS, Goldstein JL. Insulin inhibits transcription of IRS-2 gene in rat liver through an insulin response element (IRE) that resembles IREs of other insulin-repressed genes. Proceedings of the National Academy of Sciences 2001;98(7):3756-61. doi: 10.1073/pnas.071054598.
  27. Hirashima Y, Tsuruzoe K, Kodama S, Igata M, Toyonaga T, Ueki K, et al. Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway. Journal of Endocrinology 2003;179(2):253-66. doi: 10.1677/joe.0.1790253.
  28. Stanley J. The regulation of glucose production: The role of liver glycogen and gluconeogenesis in the liver and kidney cortex. British Journal of Anaesthesia 1981;53(2):137-46. doi: 10.1093/bja/53.2.137.
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