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. 2024;27(1):31-38.
doi: 10.22038/IJBMS.2023.68739.14981.

Fucoidan alleviated autoimmune diabetes in NOD mice by regulating pancreatic autophagy through the AMPK/mTOR1/TFEB pathway

Haiqi Gao  1   2 , Yifan Zhou  3   2 , Chundong Yu  4 , Guifa Wang  1 , Wenwei Song  1 , Zixu Zhang  1 , Lu Lu  1 , Meilan Xue  1 , Hui Liang  5
Affiliations

Fucoidan alleviated autoimmune diabetes in NOD mice by regulating pancreatic autophagy through the AMPK/mTOR1/TFEB pathway

Haiqi Gao et al. Iran J Basic Med Sci. 2024.

Abstract

Objectives: The present study investigated the effect and its underlying mechanisms of fucoidan on Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice.

Materials and methods: Twenty 7-week-old NOD mice were used in this study, and randomly divided into two groups (10 mice in each group): the control group and the fucoidan treatment group (600 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 5 weeks. The proportions of Th1/Th2 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 T1DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th1/Th2 cells ratio and decreased Th1 type pro-inflammatory cytokines' level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-1 and LC3B II/LC3B I. The expression of p-AMPK was up-regulated and p-mTOR1 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-9, cleaved caspase-3, and Bax were up-regulated after fucoidan treatment.

Conclusion: Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR1/TFEB pathway in pancreatic cells.

Keywords: Apoptosis; Autophagy; Fucoidan; NOD mice; Type 1 diabetes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Effect of fucoidan on weight gain, blood glucose levels, and glucose tolerance in NOD mice. (A) Weight gain, (B) Blood glucose level, (C) Glucose tolerance. The data were presented as mean values of n=10 animals/group ± SD. *P<0.05 vs the control group; **P<0.01 vs the control group
Figure 2
Figure 2
Effect of fucoidan on pancreas structure of non-obese diabetic (NOD) mice
Figure 3
Figure 3
Levels o f inflammation factors of non-obese diabetic (NOD) mice
Figure 4
Figure 4
Effect of fucoidan on pancreatic cell apoptosis of mice
Figure 5
Figure 5
Effect of fucoidan on molecules of autophagy pathway in mice
See this image and copyright information in PMC

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