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 |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Agonist
Adiponectin receptor 1 biology Chemistry medicine.drug_class Nutrition. Foods and food supply Glucose uptake Public Health Environmental and Occupational Health Glucose transporter AMPK TP368-456 Food processing and manufacture Article Cell biology AdipoRon chemistry.chemical_compound biology.protein medicine TX341-641 Receptor Peptides GLUT4 Food Science Nutrition |
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 |
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