Study of the effects and mechanisms of brown algae extracts on pancreatic beta-cell dysfunction and nephropathy under diabetic condition

• Main Authors: Wen-Chun Yu, 余文鈞
• Other Authors: Tz-Chong Chou
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/nte63m

博士 === 國防醫學院 === 生命科學研究所 === 106 === The rapidly increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide has become one of the most serious health problems. T2DM is characterized by insulin resistance (impaired response to insulin) and -cell dysfunction (failure to produce sufficient insulin). Diabetic nephropathy (DN) is a serious complication of T2DM that affects glomerular, tubular structure, and interstitial cells of the kidneys. Under hyperglycemia condition, increased advanced glycation end products (AGEs) formation can activate its receptor of AGE (RAGE)-mediated upregulation of transforming growth factor beta (TGF-), thereby causing renal fibrosis. Fucoidan (FO), extracted from brown algae, has several biological functions, including anti-cancer, anti-inflammatory activities. However, whether FO has protective effect against pancreatic -cell damage and impaired insulin formation under diabetic condition, as well as DN are still unclear. Therefore, we designed 2 parts of researches to investigate the two important issues. Part 1: We demonstrated that treatment with FO significantly attenuated -cell apoptosis and dysfunction accompanied by elevation of insulin formation in STZ-treated -cell and mice. The beneficial effects of FO may be mediated by increase of Sirt-1 expression and activity and then activation of PDX-1 and GLP-1R expression. Part 2: In AGE-treated renal tubular cells, FO treatment greatly increased Sirt-1 expression but inhibited RAGE, HMGB1 and TGF- expression, and the events can be attenuated by addition of Sirt-1 inhibitor (Ex527), significantly. Consistently, the abnormal features, including high cholesterol, TG levels, HDL/LDL, proteinuria, renal dysfunction, changes of renal structure, elevation of RAGE and TGF- expression high fat diet (HFD) and STZ/NA induced DN mice model were markedly improved by treatment with FO. In conclusion, we demonstrated that FO has an anti-diabetes mainly through attenuating -cell apoptosis and increasing insulin secretion. Moreover, FO greatly protects high fat diet and STZ/NA induced DN by inhibiting AGE/RAGE/NF-kB/TGF- signaling. Notably, these beneficial effects of FO on pancreatic  cells and DN may be regulated by upregulation of Sirt1. Therefore, FO-containing food or supplements may exhibit a therapeutic effect on diabetes and related DN.