Polygonatum sibiricum polysaccharide (PSP) has been shown to alleviate hyperglycemia and reduce oxidative stress to delay the progression of diabetic retinopathy and cataracts. However, its role and underlying mechanisms in regulating type 2 diabetes mellitus (T2DM) remain unclear. Nuclear factor erythroid 2‑related factor 2 (Nrf2) activation plays a protective role in T2DM. The present study focused on the effect of PSP on inflammatory cytokine secretion and Nrf2 expression in the adipocytes of T2DM patients. In this study, high‑glucose‑ and high‑insulin‑induced 3T3‑L1 adipocytes were used to mimic insulin‑resistant (IR)‑3T3‑L1 adipocytes. Furthermore, the effect and underlying mechanisms of PSP on inflammation and glucose uptake in IR‑3T3‑L1 adipocytes were investigated. The present study found that proliferation after 50, 100 and 250 µg/ml PSP treatment had no significant change in normal 3T3‑L1 adipocytes. A total of 50, 100 and 250 µg/ml of PSP also alleviated IL‑1β, IL‑6, and TNF‑α levels and promoted proliferation, glucose uptake, and glucose transporter 4 expression in IR‑3T3‑L1 adipocytes. Furthermore, 50, 100 and 250 µg/ml PSP promoted Nrf2 and HO‑1 expression. However, silencing Nrf2 expression reversed the effect of 100 µg/ml PSP in IR‑3T3‑L1 adipocytes. In conclusion, these results suggest that PSP alleviates inflammatory cytokines and promotes glucose uptake in IR‑3T3‑L1 adipocytes by promoting Nrf2 expression. PSP may be a potential therapeutic agent for T2DM treatment by promoting Nrf2 expression.
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