Type 2 diabetes mellitus (T2DM) accounts for more than 90% of cases of diabetes mellitus, which is harmful to human health. Herein, neoagaro-oligosaccharides (NAOs) were prepared and their potential as a treatment of T2DM was evaluated in KunMing (KM) mice. Specifically, a T2DM mice model was established by the combination of a high-fat diet (HFD) and alloxan injection. Consequently, the mice were given different doses of NAOs (100, 200, or 400 mg/kg) and the differences among groups of mice were recorded. As a result of the NAOs treatment, the fasting blood glucose (FBG) was lowered and the glucose tolerance was improved as compared with the model group. As indicated by the immunohistochemistry assay, the NAOs treatment was able to ameliorate hepatic macrovesicular steatosis and hepatocyte swelling, while it also recovered the number of pancreatic β-cells. Additionally, NAOs administration benefited the antioxidative capacity in mice as evidenced by the upregulation of both glutathione peroxidase and superoxide dismutase activity and the significant reduction of the malondialdehyde concentration. Furthermore, NAOs, as presented by Western blotting, increased the expression of p-ERK1/2, p-JNK, NQO1, HO-1, and PPARγ, via the MAPK, Nrf2, and PPARγ signaling pathways, respectively. In conclusion, NAOs can be used to treat some complications caused by T2DM, and are beneficial in controlling the level of blood glucose and ameliorating the damage of the liver and pancreatic islands.
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