Fucoidan alleviated autoimmune diabetes in NOD mice by regulating pancreatic autophagy through the AMPK/mTOR۱/TFEB pathway

Objective(s): The present study investigated the effect and its underlying mechanisms of fucoidan on Type ۱ diabetes mellitus (T۱DM) in non-obese diabetic (NOD) mice. Materials and Methods: Twenty ۷-week-old NOD mice were used in this study, and randomly divided into two groups (۱۰ mice in each group): the control group and the fucoidan treatment group (۶۰۰ mg/kg. body weight). The weight gain, glucose tolerance, and fasting blood glucose level in NOD mice were detected to assess the development of diabetes. The intervention lasted for ۵ weeks. The proportions of Th۱/Th۲ cells from spleen tissues were tested to determine the anti-inflammatory effect of fucoidan. Western blot was performed to investigate the expression levels of apoptotic markers and autophagic markers. Apoptotic cell staining was visualized through TdT-mediated dUTP nick-end labeling (TUNEL). Results: The results suggested that fucoidan ameliorated T۱DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th۱/Th۲ cells ratio and decreased Th۱ type pro-inflammatory cytokines’ level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-۱ and LC۳B II/LC۳B I. The expression of p-AMPK was up-regulated and p-mTOR۱ was inhibited, which promoted the nucleation of transcription factor EB (TFEB), leading to autophagy. Moreover, fucoidan induced apoptosis of pancreatic tissue cells. The levels of cleaved caspase-۹, cleaved caspase-۳, and Bax were up-regulated after fucoidan treatment.  Conclusion: Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR۱/TFEB pathway in pancreatic cells.

Keywords:

Apoptosis , Autophagy , Fucoidan , NOD mice , Type ۱ diabetes