Modulation of Insulin Resistance by Dihydromyricetin in T2DM Rats

Endoplasmic reticulum stress (ERS) is an important link leading to the occurrence of insulin resistance (IR). The study aimed to investigate the role of Chinese medicine Dihydromyricetin (DHM) in IR in HepG2 cells and type 2 diabetes mellitus (T2DM) rats and its possible mechanism under the participation of ERS. HepG2 cells were treated with 5×10−6 mol/L insulin to establish an IR cell model. T2DM rats were established through the combination of low-dose streptozocin (STZ) and a high-fat diet. T2DM rats were given low doses (DHM-L) or high doses (DHM-H) of DHM. OGTT was performed for the glucose tolerance evaluation. Western blot was done for the protein detection. DHM improved the insulin sensitivity, lipid levels, and inflammatory response in HepG2 cells induced by IR. DHM decreased the body weight, FBG, FINS, and HOMA-IR of T2DM rats. OGTT test demonstrated the increase of blood glucose and area under the curve (AUC) in T2DM rats, which was reduced by DHM treatment in a dosed manner. The increased TC, TG, LDL, and reduced HDL in T2DM rats were reversed by DHM, which is related to the improvement of lipid metabolism. For mechanism, DHM inhibited the ERS signaling and inflammatory response. DHM attenuates IR and lipid metabolism in a dose-dependent manner in T2DM rats, and the mechanism might be related to improving liver ERS and inhibiting inflammation.