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

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. Goto­Kakizaki (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 RIN­5F rat insulin­secreting cell line was treated with fucoidan in high glucose conditions, following which the dose­dependent and time­dependent 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 RIN­5F cells, and the insulin secretion increased significantly in a dose­ and time­dependent 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 fucoidan­treated RIN­5F cells, and this increase was dose­ and time­dependent. In addition, treatment with a phosphodiesterase inhibitor, which decreases the degradation of cAMP, significantly increased fucoidan­induced insulin secretion, whereas treatment with an adenylyl cyclase inhibitor, which decreases the generation of cAMP, significantly decreased fucoidan­induced 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.