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Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats

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Abstract

The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups: control group, non-diabetic obese group and type 2 diabetic group (n=20 each). The rats were evaluated physiologically and biochemically. The hepatic histopathological changes were observed using haematoxylin and eosin (HE) staining. The mRNA expression patterns of hepcidin, interleukin-6 (IL-6), hypoxia-inducible factor (HIF) and ferroportin (Fpn) in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further analyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly (P<0.001). However, there was no significant difference in soluble transferring receptor (sTfR):ferritin ratio among the three groups (P>0.05). The real-time RT-PCR, immunohistochemistry and Western blotting results all revealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group (P<0.001). The expression levels of hepcidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant difference (P>0.05). However, the protein expression levels of hepcidin in type 2 diabetic group were significantly higher than those in non-diabetic obese group (P<0.05). Compared to control group, the expression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels of Fpn mRNA decreased (P<0.05). However, the expression levels of HIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal expression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron release from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.

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References

  1. Shaw JE, Sicree RA, Zimmet PZ, et al. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract, 2010,87(1):4–14

    Article  CAS  PubMed  Google Scholar 

  2. Lukic L, Lalic NM, Rajkovic N, et al. Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL-6 cytokine levels: potential targets for an efficient preventive intervention. Int J Environ Res Public Health, 2014,11(4):3586–3598

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Bao W, Rong Y, Rong S, et al. Dietary iron intake, body iron stores, and the risk of type 2 diabetes: a systematic review and meta-analysis. BMC Med, 2012,10:119

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Dulal HP, Lamsal M, Sharma SK, et al. Status of iron, oxidant and antioxidants in chronic type 2 diabetes mellitus patients. Nepal Med Coll J, 2014,16(1):54–57

    CAS  PubMed  Google Scholar 

  5. Wang X, Fang X, Wang F, et al. Pleiotropic actions of iron balance in diabetes mellitus. Rev Endocr Metab Disord, 2015,16(1):15–23

    Article  CAS  PubMed  Google Scholar 

  6. Rishi G, Wallance DF, Subramaniam VN. Hepcidin: Regulation of the master iron regulator. Biosci Reports, 2015,35(3):e00192

    Article  Google Scholar 

  7. Diehl AM, Goodman Z, Ishak KG. Alcohol-like liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology, 1988,95(4):1056–1062

    CAS  Google Scholar 

  8. Knodell RG, Ishak KG, Wollman J. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology, 1981,1(5):431–435.

    Article  CAS  PubMed  Google Scholar 

  9. Jalali MT, Mohseni A, Latifi M, et al. Evaluation of diagnostic efficacy of serum sTfR assay in iron-deficiency anemia and Beta-thalassemia trait in Shafa hospital, Ahvaz, Iran 2010. Eur Rev Med Phamacol Sci, 2012,16(10): 1441–1445

    CAS  Google Scholar 

  10. Xian S, Zhu CH, Wei MY, et al. Relationship between the activation of hepatic stellate cell and the early stage of liver fibrosis in experimental diabetic tree shrews. Basic Clin Med, 2006,26(6):621–625

    Google Scholar 

  11. Abboud S, Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem, 2000,275(26):19906–19912

    Article  CAS  PubMed  Google Scholar 

  12. Ivan DD, Diane MW, Jerry K, et al. The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell, 2007,18(7):2569–2578

    Article  Google Scholar 

  13. Bozzini C, Girelli D, Olivieri O, et al. Prevalence of body iron excess in the metabolic syndrome. Diabetes Care, 2005,28(8):2061–2063

    Article  PubMed  Google Scholar 

  14. Sheu WH, Chen YT, Lee WJ, et al. A relationship between serum ferritin and the insulin resistance syndrome is present in non-diabetic women but not in non-diabetic men. Clin Endocrinol (Oxf), 2003,58(3):380–385

    Article  CAS  Google Scholar 

  15. Jiang R, Manson JE, Meigs JB, et al. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA, 2004,291(6):711–717

    Article  CAS  PubMed  Google Scholar 

  16. Jehn ML, Guallar E, Clark JM, et al. A prospective study of plasma ferritin level and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol, 2007,165(9):1047–1054

    Article  PubMed  Google Scholar 

  17. Dongiovanni P, Fracanzani AL, Fargion S, et al. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. J Hepatol, 2011,55(4):920–932

    Article  CAS  PubMed  Google Scholar 

  18. Rajpathak SN, Crandall JP, Wylie-Rosett J, et al. The role of iron in type 2 diabetes in humans. Biochim Biophys Acta, 2009,1790(7):671–681

    Article  CAS  PubMed  Google Scholar 

  19. Kalantar-Zadeh K, Regidor DL, McAllister CJ, et al. Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol, 2005,16(10): 3070–3080

    Article  CAS  PubMed  Google Scholar 

  20. Yanoff LB, Menzie CM, Denkinger B, et al. Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes (Lond), 2007,31(9):1412–1419

    Article  CAS  Google Scholar 

  21. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest, 2004,113(9):1271–1276

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Prince OD, Langdon JM, Layman AJ, et al. Late stage erythroid precursor production is impaired in mice with chronic inflammation. Haematologica, 2012, 97(11):1648–1656

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Nath B, Szabo G. Hypoxia and hypoxia inducible factors: diverse roles in liver diseases. Hepatology, 2012,55(2): 622–633

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Xiao H, Gu Z, Wang G, et al. The possible mechanisms underlying the impairment of HIF-1a pathway signaling in hyperglycemia and the beneficial effects of certain therapies. Int J Med Sci, 2013,10(10):1412–1421

    Article  PubMed Central  PubMed  Google Scholar 

  25. Gao W, Ferguson G, Connell P, et al. Glucose attenuates hypoxia-induced changes in endothelial cell growth by inhibiting HIF-1a expression. Diab Vasc Dis Res, 2014,11(4): 270–280

    Article  CAS  PubMed  Google Scholar 

  26. Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature, 2000, 403(6771):776–781

    Article  CAS  PubMed  Google Scholar 

  27. McKie AT, Marciani P, Rolfs A, et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell, 2000,5:299–309

    Article  CAS  PubMed  Google Scholar 

  28. Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am J Physiol Gastrointest Liver Physiol, 2006,290(2):G199–G203

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China

    Yue Chen  (陈 跃), Hui-qing Yin  (阴慧清), Hao-ling Liu  (刘昊凌), Lei Xiu  (修 磊) & Xiao-yu Peng  (彭晓宇)

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  1. Yue Chen  (陈 跃)
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  2. Hui-qing Yin  (阴慧清)
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  3. Hao-ling Liu  (刘昊凌)
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  4. Lei Xiu  (修 磊)
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  5. Xiao-yu Peng  (彭晓宇)
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Correspondence to Hui-qing Yin  (阴慧清).

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Chen, Y., Yin, Hq., Liu, Hl. et al. Hepcidin and iron metabolism in non-diabetic obese and type 2 diabetic rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 851–857 (2015). https://doi.org/10.1007/s11596-015-1517-z

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  • DOI: https://doi.org/10.1007/s11596-015-1517-z

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