In vitro and in silico characterization of adiponectin-receptor agonist dipeptides

Autor: Kenta Sakai, Akihiro Nakano, Yuna Lee, Mitsuru Tanaka, Toshiro Matsui, Saya Nakamura, Noriatsu Shigemura, Keisuke Sanematsu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: NPJ Science of Food
npj Science of Food, Vol 5, Iss 1, Pp 1-10 (2021)
ISSN: 2396-8370
Popis: The aim of this study is to develop a dipeptide showing an adiponectin receptor 1 (AdipoR1) agonistic effect in skeletal muscle L6 myotubes. Based on the structure of the AdipoR1 agonist, AdipoRon, 15 synthetic dipeptides were targeted to promote glucose uptake in L6 myotubes. Tyr-Pro showed a significant increase in glucose uptake among the dipeptides, while other dipeptides, including Pro-Tyr, failed to exert this effect. Tyr-Pro induces glucose transporter 4 (Glut4) expression in the plasma membrane, along with adenosine monophosphate-activated protein kinase (AMPK) activation. In AdipoR1-knocked down cells, the promotion by Tyr-Pro was ameliorated, indicating that Tyr-Pro may directly interact with AdipoR1 as an agonist, followed by the activation of AMPK/Glut4 translocation in L6 myotubes. Molecular dynamics simulations revealed that a Tyr-Pro molecule was stably positioned in the two potential binding pockets (sites 1 and 2) of the seven-transmembrane receptor, AdipoR1, anchored in a virtual 1-palmitoyl-2-oleoyl-phosphatidylcholine membrane. In conclusion, we demonstrated the antidiabetic function of the Tyr-Pro dipeptide as a possible AdipoR1 agonist.
Databáze: OpenAIRE