Antidiabetic Effect And Mechanism Of BDDE

Objective Protein tyrosine phosphatase 1B(PTP1B) is a novel therapeutic target for type-2 diabetes, which negatively regulates the insulin signaling transduction. Bis(2, 3-dibromo-4, 5-dihydroxybenzyl) ether(BDDE), a novel bromophenol isolated from the Red Alga, is a novel PTP1 B inhibitor. But the anti-diabetic effects are not clear. In the present study, we evaluated the in vitro and in vivo antidiabetic effects of BDDE.Methods 1.The insulin-resistant Hep G2 cells were used to evaluate the in vitro antidiabetic effects of BDDE. MTT assay was used to determine the safety concentrations in Hep G2 cells. Glucose assay kit was used to check glucose uptake after treated with BDDE. Western blotting assay was used to explore the potent mechanisms. 2. The db/db mice were used to evaluate the in vivo antidiabetic effects of BDDE. Body weight, blood glucose, Glycated hemoglobin(Hb A1c), lipid profile, and insulin level were checked at the respective time points. Gastrocnemii were dissected and used to analyze the PTP1 B and insulin receptor β(IRβ) expression.Results 1. BDDE increased the insulin-resisted glucose uptake in Hep G2 cells. BDDE also decreased the expression of PTP1 B and activated the substrates and downstream signals in insulin signal pathway, such as IRβ, insulin receptor substrate-1/2(IRS1/2), phosphoinositide 3-kinase(PI3K), and protein kinase B(PKB/Akt). 2. In the db/db mice model, BDDE significantly decreased the blood glucose, Hb A1ctriglyceride(TG) and total cholesterol(TC) levels. BDDE also decreased the expression of PTP1 B and activated the phosphorylation of IRβ in gastrocnemii. Moreover, BDDE at high doses down regulated the body weight compared to metformin.Conclusion Our results suggest that BDDE as a new PTP1 B inhibitor improves glucose metabolism by stimulating the insulin signaling and could be used in the treatment of type-2 diabetes mellitus.