Effects of a natural PTP1B inhibitor from Rhodomela confervoides on the amelioration of fatty acid-induced insulin resistance in hepatocytes and hyperglycaemia in STZ-induced diabetic rats.

Abstract

PTP1B is a key negative regulator of insulin signaling transduction, and the inhibition of PTP1B has emerged as a potential therapeutic strategy to treat T2DM. 3,4-Dibromo-5-(2-bromo-6-(ethoxymethyl)-3,4-dihydroxybenzyl)benzene-1,2-diol (BPN), a natural bromophenol isolated from marine red alga Rhodomela confervoides, was found to inhibit PTP1B activity in our previous study. Herein, we identified that BPN functioned as a competitive PTP1B inhibitor and enhanced phosphorylation of IRβ, IRS-1 and Akt in palmitate acid-induced insulin-resistant HepG2 cells. Moreover, 2-deoxyglucose uptake technology-based characterization demonstrated that BPN could stimulate glucose uptake in HepG2 cells. Furthermore, the effects of BPN against oxidative stress were investigated and showed that BPN attenuated oxidative stress by attenuating ROS generation. Finally, long-term oral administration of BPN at dose of 20 mg kg−1 significantly reduced blood glucose levels in streptozotocin-induced diabetic mice and no visible toxic effects were observed. Our work is thus expected to provide a natural uncharged PTP1B inhibitor that could be used as a potential lead compound for further research.