Fucoidan ameliorates pancreatic β-cell death and impaired insulin synthesis in streptozotocin-treated β cells and mice via a Sirt-1-dependent manner

Scope: Several beneficial biological functions of fucoidan (FO) isolated from brown algae have been demonstrated. The purpose of this study was to investigate whether FO derived from Sargassum hemiphyllum ameliorates pancreatic β-cell damage and impaired insulin synthesis under diabetic condition. Methods and results: The effects of FO were studied in streptozotocin (STZ)-treated pancreatic β-cell line, NIT-1cells, and mice. The cell apoptosis, protein analyses, histological examination, and pancreatic function assays were performed. The increased pancreatic β-cell apoptosis and decreased insulin secretion observed in STZ-treated NIT-1 cells and mice were greatly attenuated by FO. Moreover, FO has an ability to enhance glucagon-like peptide-1 receptor (GLP-1R) and sirtuin 1 (Sirt-1) activity through activation of AMPK/GAPDH/PDX-1 cascade in STZ-treated β cells. However, the effects of FO were significantly reversed by EX527, a specific Sirt-1 inhibitor. Similarly, the hyperglycemia, lower expression of Sirt-1, PDX-1, and GLP-1R in the pancreas of diabetic mice were markedly improved after FO administration. Conclusion: We demonstrated that FO exhibits an anti-diabetic effect mainly through attenuation of β-cell death, thereby elevating insulin synthesis by upregulating PDX-1 and GLP1-R via a Sirt-1-dependent manner. Therefore, FO-containing food or supplements may have a therapeutic effect for diabetes by preventing β-cell damage and dysfunction.