Effects of fucoidan on insulin stimulation and pancreatic protection via the cAMP signaling pathway in vivo and in vitro

Jiang,Xiaoming; Yu,Jinfeng; Ma,Zhi; Zhang,Hong; Xie,Fengjie

doi:10.3892/mmr.2015.3989

Effects of fucoidan on insulin stimulation and pancreatic protection via the cAMP signaling pathway in vivo and in vitro

Authors:
- Xiaoming Jiang
- Jinfeng Yu
- Zhi Ma
- Hong Zhang
- Fengjie Xie
View Affiliations

Affiliations: Department of Critical Care Medicine, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Pediatric Medicine, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Pediatric Surgery Medicine, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China
Published online on: June 23, 2015 https://doi.org/10.3892/mmr.2015.3989
Pages: 4501-4507

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Diabetes is a global disease, in which pancreatic dysfunction is an important pathological process. In previous years, interest in the biological activities of seaweed has increased. Fucoidan is an extract of the seaweed Fucus vesiculosus, which has been widely investigated. The present study aimed to determine the effects of fucoidan on insulin stimulation and pancreatic protection in vivo and in vitro. Goto‑Kakizaki (GK) rats were provided with free access to standard food, with or without fucoidan, for 13 weeks, following which the body weights, and blood glucose and serum insulin levels of the rats were measured. Wistar rats were used as a control. In addition, the RIN‑5F rat insulin‑secreting cell line was treated with fucoidan in high glucose conditions, following which the dose‑dependent and time‑dependent effects of fucoidan were determined, and the concentration of insulin was measured. Glybenclamide was used as a positive control. In vivo, the body weight and serum insulin levels decreased, whereas blood glucose levels increased significantly in the GK rats, compared with the Wistar control rats. Although, fucoidan did not improve changes in body weight, the increased blood glucose levels were reduced and the decreased serum insulin levels were increased in the GK rats following oral administration of fucoidan. In vitro, fucoidan did not exhibit significant cytotoxicity towards the RIN‑5F cells, and the insulin secretion increased significantly in a dose‑ and time‑dependent manner. Treatment with amylin, an islet amyloid polypeptide and glybenclamide inhibitor, did not inhibit the stimulatory activity of fucoidan. The results of the present study also demonstrated that the concentration of cyclic adenosine monophosphate (cAMP) was significantly increased in the fucoidan‑treated RIN‑5F cells, and this increase was dose‑ and time‑dependent. In addition, treatment with a phosphodiesterase inhibitor, which decreases the degradation of cAMP, significantly increased fucoidan‑induced insulin secretion, whereas treatment with an adenylyl cyclase inhibitor, which decreases the generation of cAMP, significantly decreased fucoidan‑induced insulin secretion. In conclusion, these data indicated that fucoidan may stimulate insulin secretion and provide pancreatic protection via the cAMP signaling pathway, in vivo and in vitro.

View Figures

View References

1	Fang Y, Tian X, Bai S, Fan J, Hou W, Tong H and Li D: Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway. Int J Mol Med. 30:85–92. 2012.PubMed/NCBI
2	Tsur A, Harman-Bohem I, Buchs AE, Raz I and Wainstein J: The guidelines for the diagnosis prevention and treatment of type 2 diabetes mellitus - 2005. Harefuah. 145:583–586. 6302006.In Hebrew.
3	Genuth S: Management of the adult onset diabetic with sulfonylurea drug failure. Endocrinol Metab Clin North Am. 21:351–370. 1992.PubMed/NCBI
4	Onofrejová L, Vasícková J, Klejdus B, Stratil P, Misurcová L, Krácmar S, Kopecký J and Vacek J: Bioactive phenols in algae: The application of pressurized-liquid and solid-phase extraction techniques. J Pharm Biomed Anal. 51:464–470. 2010. View Article : Google Scholar
5	Li X, Zhao H, Wang Q, Liang H and Jiang X: Fucoidan protects ARPE-19 cells from oxidative stress via normalization of reactive oxygen species generation through the Ca²⁺-dependent ERK signaling pathway. Mol Med Rep. 11:3746–3752. 2015.PubMed/NCBI
6	Zhang P, Bi C, Schmitt SM, Li X, Fan Y, Zhang N and Dou QP: Metal-based 2,3-indolinedione derivatives as proteasome inhibitors and inducers of apoptosis in human cancer cells. Int J Mol Med. 34:870–879. 2014.PubMed/NCBI
7	Myers SP, O'Connor J, Fitton JH, Brooks L, Rolfe M, Connellan P, Wohlmuth H, Cheras PA and Morris C: A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex. Biologics. 5:45–60. 2011.PubMed/NCBI
8	Li C, Gao Y, Xing Y, Zhu H, Shen J and Tian J: Fucoidan, a sulfated polysaccharide from brown algae, against myocardial ischemia-reperfusion injury in rats via regulating the inflammation response. Food Chem Toxicol. 49:2090–2095. 2011. View Article : Google Scholar : PubMed/NCBI
9	Hernández-Corona DM, Martínez-Abundis E and González-Ortiz M: Effect of fucoidan administration on insulin secretion and insulin resistance in overweight or obese adults. J Med Food. 17:830–832. 2014. View Article : Google Scholar : PubMed/NCBI
10	Eliza J, Daisy P, Ignacimuthu S and Duraipandiyan V: Antidiabetic and antilipidemic effect of eremanthin from Costus speciosus (Koen.)Sm., in STZ-induced diabetic rats. Chem Biol Interact. 182:67–72. 2009. View Article : Google Scholar : PubMed/NCBI
11	Henquin JC: The dual control of insulin secretion by glucose involves triggering and amplifying pathways in β-cells. Diabetes Res Clin Pract. 93(Suppl 1): S27–S31. 2011. View Article : Google Scholar
12	Damdindorj B, Dezaki K, Kurashina T, Sone H, Rita R, Kakei M and Yada T: Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells. FEBS Lett. 586:2555–2562. 2012. View Article : Google Scholar : PubMed/NCBI
13	Furman B, Ong WK and Pyne NJ: Cyclic AMP signaling in pancreatic islets. Adv Exp Med Biol. 654:281–304. 2010. View Article : Google Scholar : PubMed/NCBI
14	Meenakshi S, Umayaparvathi S, Saravanan R, Manivasagam T and Balasubramanian T: Hepatoprotective effect of fucoidan isolated from the seaweed Turbinaria decurrens in ethanol intoxicated rats. Int J Biol Macromol. 67:367–372. 2014. View Article : Google Scholar : PubMed/NCBI
15	Kim CS, Sohn EJ, Kim YS, Jung DH, Jang DS, Lee YM, Kim DH and Kim JS: Effects of KIOM-79 on hyperglycemia and diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats. J Ethnopharmacol. 111:240–247. 2007. View Article : Google Scholar
16	Lan T, Shen X, Liu P, Liu W, Xu S, Xie X, Jiang Q, Li W and Huang H: Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway. Arch Biochem Biophys. 502:112–120. 2010. View Article : Google Scholar : PubMed/NCBI
17	Zhang D, Fujii I, Lin C, Ito K, Guan H, Zhao J, Shinohara M and Matsukura M: The stimulatory activities of polysaccharide compounds derived from algae extracts on insulin secretion in vitro. Biol Pharm Bull. 31:921–924. 2008. View Article : Google Scholar : PubMed/NCBI
18	Xie P, Nishiura H, Semba U, Chen J, Zhao R, Kuniyasu A and Yamamoto T: Inhibitory effects of C4a on chemoattractant and secretagogue functions of the other anaphylatoxins via Gi protein-adenylyl cyclase inhibition pathway in mast cells. Int Immunopharmacol. 12:158–168. 2012. View Article : Google Scholar
19	Hall GM and Ruggier R: Diabetes mellitus and anaesthesia. Curr Opin Anaesthesiol. 12:343–347. 1999. View Article : Google Scholar
20	Parker JC: Troglitazone: The discovery and development of a novel therapy for the treatment of Type 2 diabetes mellitus. Adv Drug Deliv Rev. 54:1173–1197. 2002. View Article : Google Scholar : PubMed/NCBI
21	Fukahori S, Yano H, Akiba J, Ogasawara S, Momosaki S, Sanada S, Kuratomi K, Ishizaki Y, Moriya F, Yagi M and Kojiro M: Fucoidan, a major component of brown seaweed, prohibits the growth of human cancer cell lines in vitro. Mol Med Rep. 1:537–542. 2008.PubMed/NCBI
22	Samarasinghe S and Vokes T: Diabetes insipidus. Expert Rev Anticancer Ther. 6(Suppl 9): S63–S74. 2006. View Article : Google Scholar : PubMed/NCBI
23	Jacques-Silva MC, Correa-Medina M, Cabrera O, Rodriguez-Diaz R, Makeeva N, Fachado A, Diez J, Berman DM, Kenyon NS, Ricordi C, et al: ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic beta cell. Proc Natl Acad Sci USA. 107:6465–6470. 2010. View Article : Google Scholar : PubMed/NCBI
24	Hölscher C: The incretin hormones glucagonlike peptide 1 and glucose-dependent insulinotropic polypeptide are neuroprotective in mouse models of Alzheimer's disease. Alzheimers Dement. 10(1 Suppl): S47–S54. 2014. View Article : Google Scholar : PubMed/NCBI
25	Ma Y, Luo T, Xu W, Ye Z and Hong A: A new recombinant pituitary adenylate cyclase-activating peptide-derived peptide efficiently promotes glucose uptake and glucose-dependent insulin secretion. Acta Biochim Biophys Sin (Shanghai). 44:948–956. 2012. View Article : Google Scholar
26	Widenmaier SB, Ao Z, Kim SJ, Warnock G and McIntosh CH: Suppression of p38 MAPK and JNK via Akt-mediated inhibition of apoptosis signal-regulating kinase 1 constitutes a core component of the beta-cell pro-survival effects of glucose-dependent insulinotropic polypeptide. J Biol Chem. 284:30372–30382. 2009. View Article : Google Scholar : PubMed/NCBI
27	Chalon S, Vancassel S, Zimmer L, Guilloteau D and Durand G: Polyunsaturated fatty acids and cerebral function: Focus on monoaminergic neurotransmission. Lipids. 36:937–944. 2001. View Article : Google Scholar : PubMed/NCBI
28	Fedor D and Kelley DS: Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. 12:138–146. 2009. View Article : Google Scholar : PubMed/NCBI
29	Tengholm A: Cyclic AMP dynamics in the pancreatic β-cell. Ups J Med Sci. 117:355–369. 2012. View Article : Google Scholar : PubMed/NCBI