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Fucoidan isolated from the sea cucumber Acaudina molpadioides improves insulin resistance in adipocytes via activating PKB/GLUT4 pathway

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Abstract

Fucoidan was extracted from the sea cucumber Acaudina molpadioides (Am-FUC), and its effect of improving insulin resistance was investigated in vitro and in vivo. Insulin resistance model 3T3-L1 adipocytes were established by treating with 20 ng/ml TNF-α for 24 h. Am-FUC significantly increased the glucose consumption, indicating that Am-FUC improved insulin resistance. Besides, Am-FUC up-regulated PKB/GLUT4 pathway in transcriptional level, enhanced phosphorylation of PI3K and PKB, promoted GLUT4 translocation, which indicated that the pathway was activated. In in vivo experiments, insulin resistance model mice were established by feeding a high-fat high-fructose diet. Am-FUC increased serum insulin level, decreased HOMA-IR, reduced fasting blood glucose level, and improved oral glucose tolerance ability, revealing that Am-FUC can still remit the insulin resistance in vivo. The protein expression levels and phosphorylation of PI3K and PKB in adipose tissue were in keeping with that in 3T3-L1 adipocytes. Combination of Am-FUC and rosiglitazone exerted better effect on improving insulin resistance. These findings suggested that Am-FUC improved the insulin resistance by activating the PKB/GLUT4 pathway.

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Abbreviations

Am-FUC:

Fucoidan isolated from the sea cucumber Acaudina molpadioides

AUC:

Area under curve

BSA:

Bovine serum albumin

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

GLUT4:

Glucose transporter isoform 4

HFFD:

High-fat high-fructose diet

HOMA-IR:

Homeostasis model assessment of insulin resistance index

IBMX:

Isobutylmethylxanthine

IR:

Insulin receptor

IRS-1:

Insulin receptor substrate-a

PI3K:

PI3-kinase

PKB:

Protein kinase B

RSG:

Rosiglitazone

TNF-α:

Tumor necrosis factor alpha

References

  1. Wang Y, Yao M (2009) Effects of chromium picolinate on glucose uptake in insulin-resistant 3T3-L1 adipocytes involve activation of p38 MAPK. J Nutr Biochem 20:982–991

    Article  CAS  Google Scholar 

  2. Rains JL, Jain S (2011) Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 50:567–575

    Article  CAS  Google Scholar 

  3. Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, Lu H, Fantus IG, Jin T (2012) Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. Plos One 7:e28784-1-13

    Article  Google Scholar 

  4. Rask-Madsen C, Kahn CR (2012) Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease. Arterioscler Thromb Vasc Biol 32:2052–2059

    Article  CAS  Google Scholar 

  5. Jin L, Shi G, Ning G, Li X, Zhang Z (2011) Andrographolide attenuates tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes. Mol Cell Endocrinol 332:134–139

    Article  CAS  Google Scholar 

  6. Wada T, Hoshino M, Kimura Y, Ojima M, Nakano T, Koya D, Tsuneki H, Sasaoka T (2011) Both type and type IFN induce insulin resistance by inducing different isoforms of SOCS expression in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab 300:E1112–E1123

    Article  CAS  Google Scholar 

  7. Chen S, Xue C, Yin L, Tang Q, Yu G, Chai W (2011) Comparison of structures and anticoagulant activities of fucosylated chondroitin sulfates from different sea cucumbers. Carbohydr Polym 83:688–696

    Article  CAS  Google Scholar 

  8. Wang Y, Su W, Zhang C, Xue C, Chang Y, Wu X, Tang Q, Wang J (2012) Protective effect of sea cucumber (Acaudina molpadioides) fucoidan against ethanol-induced gastric damage. Food Chem 133:1414–1419

    Article  CAS  Google Scholar 

  9. Yu L, Xu X, Xue C, Chang Y, Ge L, Wang Y, Zhang C, Liu G, He C (2013) Enzymatic preparation and structural determination of oligosaccharides derived from sea cucumber (Acaudina molpadioides) fucoidan. Food Chem 139:702–709

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Xu H, Wang J, Chang Y, Xu J, Wang Y, Long T, Xue C (2014) Fucoidan from the sea cucumber Acaudina molpadioides exhibits anti-adipogenic activity by modulating the Wnt/β-catenin pathway and down-regulating the SREBP-1c expression. Food Funct 5:1547–1555

    Article  CAS  Google Scholar 

  14. Chang Y, Xue C, Tang Q, Li D, Wu X, Wang J (2009) Isolation and characterization of a sea cucumber fucoidan-utilizing marine bacterium. Lett Appl Microbiol 50:301–307

    Article  Google Scholar 

  15. Hsu HF, Tsou TC, Chao HR, Shy CG, Kuo YT, Tsai FY, Yeh SC, Ko YC (2010) Effects of arecoline on adipogenesis, lipolysis, and glucose uptake of adipocytes-A possible role of betel-quid chewing in metabolic syndrome. Toxicol Appl Pharm 245:370–377

    Article  CAS  Google Scholar 

  16. Samuel VT, Shulman GI (2012) Mechanisms for insulin resistance: common threads and missing links. Cell 148:852–871

    Article  CAS  Google Scholar 

  17. Nishikawa S, Hosokawa M, Miyashita K (2012) Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-A y mice. Phytomedicine 19:389–394

    Article  CAS  Google Scholar 

  18. Hu S, Chang Y, Wang J, Xue C, Li Z, Wang Y (2013) Fucosylated chondroitin sulfate from sea cucumber in combination with rosiglitazone improved glucose metabolism in the liver of the insulin-resistant mice. Biosci Biotechnol Biochem 77:2263–2268

    Article  CAS  Google Scholar 

  19. Lee S, Yang WK, Song JH, Ra YM, Jeong JH, Choe W, Kang I, Kim SS, Ha J (2013) Anti-obesity effects of 3-hydroxychromone derivative, a novel small-molecule inhibitor of glycogen synthase kinase-3. Biochem Pharmacol 85:965–976

    Article  CAS  Google Scholar 

  20. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A (2008) Adipogenesis and WNT signaling. Trends Endocrinol Metab 20:17–24

    Google Scholar 

  21. Zhu S, Sun F, Li W, Cao Y, Wang C, Wang Y, Liang D, Zhang R, Zhang S, Wang H, Cao F (2011) Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes. Mol Cell Biochem 353:305–313

    Article  CAS  Google Scholar 

  22. Liu M, Wu K, Mao X, Wu Y, Ouyang J (2010) Astragalus polysaccharide improves insulin sensitivity in KKAy mice: regulation of PKB/GLUT4 signaling in skeletal muscle. J Ethnopharmacol 127:32–37

    Article  CAS  Google Scholar 

  23. Berenguer M, Zhang J, Bruce MC, Martinez L, Gonzalez T, Gurtovenko AA, Xu T, Marchand-Brustel YL, Govers R (2011) Dimethyl sulfoxide enhances GLUT4 translocation through a reduction in GLUT4 endocytosis in insulin-stimulated 3T3-L1 adipocytes. Biochimie 93:697–709

    Article  CAS  Google Scholar 

  24. Wang X, Wahl R (2014) Responses of the insulin signaling pathway in the brown adipose tissue of rats following cold exposure. Plos One 9:e99772-1-8

    Google Scholar 

  25. Hsieh TJ, Hsieh PC, Wu MT, Chang WC, Hsiao PJ, Lin KD, Chou PC, Shin SJ (2011) Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes. Cell Biol Toxicol 27:397–411

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Choi SS, Cha BY, Iida K, Lee YS, Yonezawa T, Teruya T, Nagai K, Woo JT (2011) Artepillin C, as a PPARγ ligand, enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Biochem Pharmacol 81:925–933

    Article  CAS  Google Scholar 

  28. Foran PGP, Fletcher LM, Oatey PB, Mohammed N, Dolly JO, Tavare JM (1999) Protein kinase B stimulates the translocation of GLUT4 but not GLUT1 or transferrin receptors in 3T3-L1 adipocytes by a pathway involving SNAP-23, Synaptobrevin-2, and/or cellubrevin. J Biol Chem 274:28087–28095

    Article  CAS  Google Scholar 

  29. Tsuchiya A, Kanno T, Nishizaki T (2014) PI3 kinase directly phosphorylates Akt1/2 at Ser473/474 in the insulin signal transduction pathway. J Endocrinol 220:49–59

    Article  CAS  Google Scholar 

  30. Yamashita Y, Wang L, Tinshun Z, Nakaura T, Ashida H (2012) Fermented tea improves glucose intolerance in mice by enhancing translocation of glucose transporter 4 in skeletal muscle. J Agric Food Chem 60:11366–11371

    Article  CAS  Google Scholar 

  31. Fonseca V, Rosenstock J, Patwardhan R, Salzman A (2000) Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus. J Am Med Assoc 283:1695–1702

    Article  CAS  Google Scholar 

  32. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR (2003) Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. Hepatology 38:1008–1017

    Article  CAS  Google Scholar 

  33. Step SE, Lim H, Marinis JM, Prokesch A, Steger DJ, You S, Won K, Lazar MA (2014) Anti-diabetic rosiglitazone remodels the adipocyte transcriptome by redistributing transcription to PPAR-γ driven enhancers. Genes Dev 28:1018–1028

    Article  CAS  Google Scholar 

  34. Irhimeh MR, Fitton JH, Lowenthal RM, Kongtawelert P (2005) A quantitative method to detect fucoidan in human plasma using a novel antibody. Methods Find Exp Clin Pharmacol 27:705–710

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Marine Public welfare Scientific Research Project of China (No. 201105029) and the National Nature Science Foundation of China (No. 31371876).

Conflict of interest

None.

Compliance with Ethics Requirements

The use of animals in this study was approved by the ethical committee of experimental animal care at the Ocean University of China.

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Authors and Affiliations

  1. College of Food Science and Engineering, Ocean University of China, Qingdao, 266003, China

    Hui Xu, Jie Xu, Yiming Wang, Shiwei Hu, Yuming Wang, Jingfeng Wang & Changhu Xue

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  1. Hui Xu
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  2. Jie Xu
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  3. Yiming Wang
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  4. Shiwei Hu
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  5. Yuming Wang
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  6. Jingfeng Wang
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  7. Changhu Xue
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Corresponding author

Correspondence to Jingfeng Wang.

Additional information

Hui Xu and Jie Xu have contributed equally to this work.

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Xu, H., Xu, J., Wang, Y. et al. Fucoidan isolated from the sea cucumber Acaudina molpadioides improves insulin resistance in adipocytes via activating PKB/GLUT4 pathway. Eur Food Res Technol 240, 753–761 (2015). https://doi.org/10.1007/s00217-014-2380-z

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  • DOI: https://doi.org/10.1007/s00217-014-2380-z

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