Page 66 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-36]

DH047 induces insulin sensitivity and glucose uptake via

inhibition of protein tyrosine phosphatases

Dohee Ahn¹, Sun-Young Yoon¹, Ji Young Hwang¹, Sang J. Chung¹˙*

¹College of Pharmacy, Sungkyunkwan University, Suwon 16419, South Korea

Type 2 diabetes mellitus (T2DM) is a disease characterized by insulin resistance. Insulin resistance has a feature of
defects in insulin signaling and several protein tyrosine phosphatases (PTPs) involved in this signaling pathway can
be potential antidiabetic targets. We have screened natural compound to identify potent inhibitors of PTPs involved

in insulin resistance. Among them, DH047 inhibits several PTPs. Then, we examined its IC₅₀ and cooperative binding

through evaluating hill coefficient in vitro. In C2C12 myotubes and 3T3-L1 adipocytes, DH047 increased GLUT4
translocation to the plasma membrane protein and stimulates glucose uptake in a concentration-dependent manner.
In addition, we demonstrated that DH047 stimulated glucose uptake through activation of AMPK and Akt signaling

pathways. Thus, these results suggest DH047 is a potential therapeutic candidate for T2DM.