Autor: |
Yuna Lee, Akihiro Nakano, Saya Nakamura, Kenta Sakai, Mitsuru Tanaka, Keisuke Sanematsu, Noriatsu Shigemura, Toshiro Matsui |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
|
Zdroj: |
npj Science of Food, Vol 5, Iss 1, Pp 1-10 (2021) |
Druh dokumentu: |
article |
ISSN: |
2396-8370 |
DOI: |
10.1038/s41538-021-00114-2 |
Popis: |
Abstract 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: |
Directory of Open Access Journals |
Externí odkaz: |
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