Skip to main content
Log in

Fucoidan from Acaudina molpadioides protects pancreatic islet against cell apoptosis via inhibition of inflammation in type 2 diabetic mice

  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Inflammation induces pancreatic islet cell apoptosis. Effects of fucoidan from Acaudina molpadioides (Am-FUC) on inhibition of pancreatic islet cell apoptosis and inflammation in type 2 diabetic mice were investigated. Am-FUC repaired pancreatic islet cells, decreased serum C-reactive protein (CRP), macrophage inflammatory protein 1 (MIP-1), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and increased the IL-10 level. Am-FUC also reduced TNF-α, CRP, MIP-1, IL-1β, and IL-6 mRNA expressions, and increased IL-10 mRNA expression in epididymal adipose tissues. Am-FUC reduced Bid, Bax, cytochrome c, caspase 9, and caspase 3 mRNA expressions, and increased Bcl-2 and Bcl-xL mRNA expressions. Am-FUC down-regulated t-Bid, Bax, cytochrome c, and caspase 9 activities, cleaved caspase 3 proteins, and up-regulated Bcl-2 and Bcl-xL proteins. Thus, an Am-FUCblocked mitochondrial pathway was the suppression mechanism in pancreatic islet cell apoptosis via regulation of inflammatory cytokines providing dietary intervention in type 2 diabetes and inflammation-induced pancreatic islet apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Muoio DM, Newgard CB. Mechanisms of disease: Molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat. Rev. Mol. Cell Bio. 9: 193–205 (2008)

    Article  CAS  Google Scholar 

  2. Moon H, Chon J, Joo J, Kim D, In J, Lee H, Park J, Choi J. FTY720 preserved islet β-cell mass by inhibiting apoptosis and increasing survival of β-cells in db/db mice. Diabetes Metab. Res. 29: 19–24 (2013)

    Article  CAS  Google Scholar 

  3. El-Azab MF, Attia FM, El-Mowafy AM. Novel role of curcumin combined with bone marrow transplantation in reversing experimental diabetes: Effects on pancreatic islet regeneration, oxidative stress, and inflammatory cytokines. Eur. J. Pharmacol. 658: 41–48 (2011)

    Article  CAS  Google Scholar 

  4. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabete. 52: 102–110 (2003)

    Article  CAS  Google Scholar 

  5. Hou G, Li C, Liu S, Huan Y, Liu Q, Sun S, Li L, Hou S, Shen Z. Long-term treatment with EXf, a peptide analog of Exendin-4, improves β-cell function and survival in diabetic KKAy mice. Peptide. 40: 123–132 (2013)

    Article  CAS  Google Scholar 

  6. Kang JH, Tsuyoshi G, Han IS, Kawada T, Kim YM, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesit. 18: 780–787 (2010)

    Article  CAS  Google Scholar 

  7. Bouzakri K, Plomgaard P, Berney T, Donath MY, Pedersen BK, Halban PA. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle. Diabete. 60: 1111–1121 (2011)

    Article  CAS  Google Scholar 

  8. Zhang Z, Dign Y, Dai X, Wang J, Li Y. Epigallocatechin-3-gallate protects proinflammatory cytokine induced injuries in insulin-producing cells through the mitochondrial pathway. Eur. J. Pharmacol. 670: 311–316 (2011)

    Article  CAS  Google Scholar 

  9. Kara G, Cifcibasi E, Karsidag K, Cintan S. Short term effects of periodontal therapy on inflammatory markers in patients with type-2 diabetes. Saudi Med. J. 36: 469–476 (2015)

    Article  Google Scholar 

  10. Chaurio RA, Janko C, Muñoz LE, Frey B, Herrmann M, Gaipl US. Phospholipids: Key players in apoptosis and immune regulation. Molecule. 14: 4892–4914 (2009)

    Article  CAS  Google Scholar 

  11. Wilding JP. The importance of free fatty acids in the development of type 2 diabetes. Diabetic Med. 24: 934–945 (2007)

    Article  CAS  Google Scholar 

  12. Daniele G, Eldor R, Merovic A, Clarke GD, Xiong J, Tripathy D, Taranova A, Abdul-Ghani M, De Fronzo RA. Chronic reduction of plasma free fatty acid improves mitochondrial function and whole-body insulin sensitivity in obese and type 2 diabetic individuals. Diabete. 63: 2812–2820 (2014)

    Article  CAS  Google Scholar 

  13. Hu S, Chang Y, Wang J, Xue C, Shi D, Xu H, Wang Y. Fucosylated chondroitin sulfate from Acaudina molpadioides improves hyperglycemia via activation of PKB/GLUT4 signaling in skeletal muscle of insulin resistant mice. Food Funct. 4: 1639–1646 (2013)

    Article  CAS  Google Scholar 

  14. Yu L, Ge L, Xue C, Chang Y, Zhang C, Xu X, Wang Y. Structural study of fucoidan from sea cucumber Acaudina molpadioides: A fucoidan containing novel tetrafucose repeating unit. Food Chem. 142: 197–200 (2014)

    Article  CAS  Google Scholar 

  15. Chen S, Hu Y, Ye X, Li G, Yu G, Xue C, Chai W. Sequence determination and anticoagulant and antithrombotic activities of a novel sulfated fucan isolated from the sea cucumber Isostichopus badionotus. Biochim. Biophys. Act. 1820: 989–1000 (2012)

    Article  CAS  Google Scholar 

  16. Zhang Y, Song S, Song D, Liang H, Wang W, Ji A. Proliferative effects on neural stem/progenitor cells of a sulfated polysaccharide purified from the sea cucumber Stichopus japonicus. J. Biosci. Bioeng. 109: 67–72 (2010)

    Article  CAS  Google Scholar 

  17. Kim MJ, Chang UJ, Lee JS. Inhibitory effects of Fucoidan in 3T3-L1 adipocyte differentiation. Mar. Biotechnol. 11: 557–562 (2009)

    Article  CAS  Google Scholar 

  18. Kariya Y, Mulloy B, Imai K, Tominaga A, Kaneko T, Asari A, Suzuki K, Masuda H, Kyogashima M, Ishii T. Isolation and partial characterization of fucan sulfates from the body wall of sea cucumber Stichopus japonicus and their ability to inhibit osteoclastogenesis. Carbohyd. Res. 339: 1339–1346 (2004)

    Article  CAS  Google Scholar 

  19. Hu S, Xia G, Wang J, Wang Y, Li Z, Xue C. Fucoidan from sea cucumber protects against high-fat high-sucrose diet-induced hyperglycaemia and insulin resistance in mice. J. Funct. Food. 10: 128–138 (2014)

    Article  CAS  Google Scholar 

  20. Gong L, Liu F, Wang J, Wang X, Hou X, Sun Y, Qin W, Wei S, Zhang Y, Chen L, Zhang M. Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation. Biochim. Biophys. Act. 1813: 1211–1219 (2011)

    Article  CAS  Google Scholar 

  21. Allagnat F, Fukaya M, Nogueira TC, Delaroche D, Welsh N, Marselli L, Marchetti P, Haefliger JA, Haefliger JA, Eizirik DL, Cardozo AK. C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in β-cells. Cell Death Differ. 19: 1836–1846 (2012)

    Article  CAS  Google Scholar 

  22. Lin N, Chen H, Zhang H, Wan X, Su Q. Mitochondrial reactive oxygen species (ROS) inhibition ameliorates palmitate-induced INS-1 beta cell death. Endocrin. 42: 107–117 (2012)

    Article  CAS  Google Scholar 

  23. Natalicchio A, Stefano FD, Orlando MR, Melchiorre M, Leonardini A, Cignarelli A, Labarbuta R, Marchetti P, Perrini S, Laviola L, Giorgino F. Exendin-4 prevents c-Jun N-terminal protein kinase activation by tumor necrosis factor-α (TNFα) and inhibits TNFα-induced apoptosis in insulin-secreting cells. Endocrinolog. 151: 2019–2029 (2010)

    Article  CAS  Google Scholar 

  24. Lei K, Nimnual A, Zong WX, Kennedy NJ, Flavell RA, Thompson CB, Bar-Saqi D, Davis RJ. The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. Mol. Cell. Biol. 22: 4929–4942 (2002)

    Article  CAS  Google Scholar 

  25. McKenzie MD, Jamieson E, Jansen ES, Scott CL, Huang DC, Bouillet P, Allison J, Kay TW, Strasser A, Thomas HE. Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabete. 59: 644–652 (2010)

    Article  CAS  Google Scholar 

  26. Park H S, Hwang H J, Kim GY, Cha HJ, Kim WJ, Kim ND, Yoo YH, Choi YH. Induction of apoptosis by fucoidan in human leukemia U937 cells through activation of p38 MAPK and modulation of Bcl-2 family. Mar. Drug. 11: 2347–2364 (2013)

    Article  Google Scholar 

  27. Bishayee K, Ghosh S, Mukherjee A, Sadhukhan R, Mondal J, Khuda-Bukhsh AR. Quercetin induces cytochrome-c release and ROS accumulation to promote apoptosis and arrest the cell cycle in G2/M, in cervical carcinoma: Signal cascade and drug-DNA interaction. Cell Proliferat. 46: 153–163 (2013)

    Article  CAS  Google Scholar 

  28. Jiang Y, Yang J, Yang C, Meng F, Zhou Y, Yu B, Khan M, Yang H. Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via the mitochondria-related apoptotic pathway. Pharmazi. 68: 442–448 (2013)

    CAS  Google Scholar 

  29. Shamas-Din A, Bindner S, Zhu W, Zaltsman Y, Campbell C, Gross A, Leber B, Andrews DW, Fradin C. tBid undergoes multiple conformational changes at the membrane required for Bax activation. J. Biol. Chem. 288: 22111–22127 (2013)

    Article  CAS  Google Scholar 

  30. Santin I, Moore F, Colli ML, Gurzov EN, Marselli L, Marchetti P, Eizirik DL. PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim. Diabete. 60: 3279–3288 (2011)

    Article  CAS  Google Scholar 

  31. Xu X, Tu L, Jiang W, Feng W, Zhao C, Wang D. Bradykinin prevents the apoptosis of NIT-1 cells induced by TNF-a via the PI3K/Akt and MAPK signaling pathways. Int. J. Mol. Med. 29: 891–898 (2012)

    CAS  Google Scholar 

  32. Liou CM, Tsai SC, Kuo CH, Ting H, Lee SD. Cardiac Fas-dependent and mitochondria-dependent apoptosis after chronic cocaine abuse. Int. J. Mol. Sci. 15: 5988–6001 (2014)

    Article  CAS  Google Scholar 

  33. Brown JE, Dunmore SJ. Leptin decreases apoptosis and alters BCL-2: Bax ratio in clonal rodent pancreatic beta-cells. Diabetes Metab. Res. 23: 497–502 (2007)

    Article  CAS  Google Scholar 

  34. Sha H, Ma Q, Jha R, Xu F, Wang L, Wang Z, Zhao Y, Fan F. Resveratrol ameliorates hepatic injury via the mitochondrial pathway in rats with severe acute pancreatitis. Eur. J. Pharmacol. 601: 136–142 (2008)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shiwei Hu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Hu, S., Wang, J. et al. Fucoidan from Acaudina molpadioides protects pancreatic islet against cell apoptosis via inhibition of inflammation in type 2 diabetic mice. Food Sci Biotechnol 25, 293–300 (2016). https://doi.org/10.1007/s10068-016-0042-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-016-0042-6

Keywords

Navigation