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Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway

Insulin resistance (IR) is a feature of type 2 diabetes (T2DM) accompanied by reduced glucose uptake and glucose transporter 4 (GLUT4) translocation by skeletal muscle. Neuregulin-1β (NRG-1β) is essential for myogenesis and the regulation of skeletal muscle metabolism. Neuregulin-1β increases insuli...

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Autores principales: Yu, Meirong, Wu, Shuang, Gong, Chao, Chen, Lianhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871240/
https://www.ncbi.nlm.nih.gov/pubmed/36703726
http://dx.doi.org/10.3389/fphar.2022.1066279
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author Yu, Meirong
Wu, Shuang
Gong, Chao
Chen, Lianhua
author_facet Yu, Meirong
Wu, Shuang
Gong, Chao
Chen, Lianhua
author_sort Yu, Meirong
collection PubMed
description Insulin resistance (IR) is a feature of type 2 diabetes (T2DM) accompanied by reduced glucose uptake and glucose transporter 4 (GLUT4) translocation by skeletal muscle. Neuregulin-1β (NRG-1β) is essential for myogenesis and the regulation of skeletal muscle metabolism. Neuregulin-1β increases insulin sensitivity, promotes glucose uptake and glucose translocation in normal skeletal muscle. Here, we explored whether Neuregulin-1β increased glucose uptake and GLUT4 translocation in palmitate (PA)-treated C2C12 myotubes. After C2C12 myoblasts differentiated into myotubes, we used palmitate to induce cellular insulin resistance. Cells were incubated with or without Neuregulin-1β and glucose uptake was determined using the 2-NBDG assay. The expression level of glucose transporter 4 (GLUT4) was measured via immunofluorescence and Western blotting. MK2206, an inhibitor of AKT, was employed to reveal the important role played by AKT signaling in PA-treated C2C12 myotubes. We then established an animal model with T2DM and evaluated the effects of Neuregulin-1β on body weight and the blood glucose level. The GLUT4 level in the gastrocnemius of T2DM mice was also measured. NRG-1β not only increased glucose uptake by PA-treated myotubes but also promoted GLUT4 translocation to the plasma membrane. The effect of NRG-1β on PA-treated C2C12 myotubes was associated with AKT activation. In T2DM mice, Neuregulin-1β not only improved diabetes-induced weight loss and diabetes-induced hyperglycemia, but also promoted GLUT4 translocation in the gastrocnemius. In summary, Neuregulin-1β increased glucose uptake and promoted translocation of GLUT4 to the plasma membrane in PA-treated C2C12 myotubes by activating the PI3K/AKT signaling pathway.
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spelling pubmed-98712402023-01-25 Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway Yu, Meirong Wu, Shuang Gong, Chao Chen, Lianhua Front Pharmacol Pharmacology Insulin resistance (IR) is a feature of type 2 diabetes (T2DM) accompanied by reduced glucose uptake and glucose transporter 4 (GLUT4) translocation by skeletal muscle. Neuregulin-1β (NRG-1β) is essential for myogenesis and the regulation of skeletal muscle metabolism. Neuregulin-1β increases insulin sensitivity, promotes glucose uptake and glucose translocation in normal skeletal muscle. Here, we explored whether Neuregulin-1β increased glucose uptake and GLUT4 translocation in palmitate (PA)-treated C2C12 myotubes. After C2C12 myoblasts differentiated into myotubes, we used palmitate to induce cellular insulin resistance. Cells were incubated with or without Neuregulin-1β and glucose uptake was determined using the 2-NBDG assay. The expression level of glucose transporter 4 (GLUT4) was measured via immunofluorescence and Western blotting. MK2206, an inhibitor of AKT, was employed to reveal the important role played by AKT signaling in PA-treated C2C12 myotubes. We then established an animal model with T2DM and evaluated the effects of Neuregulin-1β on body weight and the blood glucose level. The GLUT4 level in the gastrocnemius of T2DM mice was also measured. NRG-1β not only increased glucose uptake by PA-treated myotubes but also promoted GLUT4 translocation to the plasma membrane. The effect of NRG-1β on PA-treated C2C12 myotubes was associated with AKT activation. In T2DM mice, Neuregulin-1β not only improved diabetes-induced weight loss and diabetes-induced hyperglycemia, but also promoted GLUT4 translocation in the gastrocnemius. In summary, Neuregulin-1β increased glucose uptake and promoted translocation of GLUT4 to the plasma membrane in PA-treated C2C12 myotubes by activating the PI3K/AKT signaling pathway. Frontiers Media S.A. 2023-01-10 /pmc/articles/PMC9871240/ /pubmed/36703726 http://dx.doi.org/10.3389/fphar.2022.1066279 Text en Copyright © 2023 Yu, Wu, Gong and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yu, Meirong
Wu, Shuang
Gong, Chao
Chen, Lianhua
Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway
title Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway
title_full Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway
title_fullStr Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway
title_full_unstemmed Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway
title_short Neuregulin-1β increases glucose uptake and promotes GLUT4 translocation in palmitate-treated C2C12 myotubes by activating PI3K/AKT signaling pathway
title_sort neuregulin-1β increases glucose uptake and promotes glut4 translocation in palmitate-treated c2c12 myotubes by activating pi3k/akt signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9871240/
https://www.ncbi.nlm.nih.gov/pubmed/36703726
http://dx.doi.org/10.3389/fphar.2022.1066279
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