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Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells
Glucose transporter 4 (GLUT4) is involved in regulating glucose uptake in striated muscle, liver, and adipose tissue. Neferine is a dibenzyl isoquinoline alkaloid derived from dietary lotus seeds and has multiple pharmacological effects. Therefore, this study investigated neferine’s role in glucose...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737894/ https://www.ncbi.nlm.nih.gov/pubmed/31551792 http://dx.doi.org/10.3389/fphar.2019.00999 |
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author | Zhao, Ping Tian, Di Song, Guanjun Ming, Qian Liu, Jia Shen, Jinhua Liu, Qing-Hua Yang, Xinzhou |
author_facet | Zhao, Ping Tian, Di Song, Guanjun Ming, Qian Liu, Jia Shen, Jinhua Liu, Qing-Hua Yang, Xinzhou |
author_sort | Zhao, Ping |
collection | PubMed |
description | Glucose transporter 4 (GLUT4) is involved in regulating glucose uptake in striated muscle, liver, and adipose tissue. Neferine is a dibenzyl isoquinoline alkaloid derived from dietary lotus seeds and has multiple pharmacological effects. Therefore, this study investigated neferine’s role in glucose translocation to cell surface, glucose uptake, and GLUT4 expression. In our study, neferine upregulated GLUT4 expression, induced GLUT4 plasma membrane fusion, increased intracellular Ca(2+), promoted glucose uptake, and alleviated insulin resistance in L6 cells. Furthermore, neferine significantly activated phosphorylation of AMP-activated protein kinase (AMPK) and protein kinase C (PKC). AMPK and PKC inhibitors blocked neferine-induced GLUT4 expression and increased intracellular Ca(2+). While neferine-induced GLUT4 expression and intracellular Ca(2+) were inhibited by G protein and PLC inhibitors, only intracellular Ca(2+) was inhibited by inositol trisphosphate receptor (IP(3)R) inhibitors. Thus, neferine promoted GLUT4 expression via the G protein-PLC-PKC and AMPK pathways, inducing GLUT4 plasma membrane fusion and subsequent glucose uptake and increasing intracellular Ca(2+) through the G protein-PLC-IP(3)-IP(3)R pathway. Treatment with 0 mM extracellular Ca(2+) + Ca(2+) chelator did not inhibit neferine-induced GLUT4 expression but blocked neferine-induced GLUT4 plasma membrane fusion and glucose uptake, suggesting the latter two are Ca(2+)-dependent. Therefore, we conclude that neferine is a potential treatment for type 2 diabetes. |
format | Online Article Text |
id | pubmed-6737894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67378942019-09-24 Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells Zhao, Ping Tian, Di Song, Guanjun Ming, Qian Liu, Jia Shen, Jinhua Liu, Qing-Hua Yang, Xinzhou Front Pharmacol Pharmacology Glucose transporter 4 (GLUT4) is involved in regulating glucose uptake in striated muscle, liver, and adipose tissue. Neferine is a dibenzyl isoquinoline alkaloid derived from dietary lotus seeds and has multiple pharmacological effects. Therefore, this study investigated neferine’s role in glucose translocation to cell surface, glucose uptake, and GLUT4 expression. In our study, neferine upregulated GLUT4 expression, induced GLUT4 plasma membrane fusion, increased intracellular Ca(2+), promoted glucose uptake, and alleviated insulin resistance in L6 cells. Furthermore, neferine significantly activated phosphorylation of AMP-activated protein kinase (AMPK) and protein kinase C (PKC). AMPK and PKC inhibitors blocked neferine-induced GLUT4 expression and increased intracellular Ca(2+). While neferine-induced GLUT4 expression and intracellular Ca(2+) were inhibited by G protein and PLC inhibitors, only intracellular Ca(2+) was inhibited by inositol trisphosphate receptor (IP(3)R) inhibitors. Thus, neferine promoted GLUT4 expression via the G protein-PLC-PKC and AMPK pathways, inducing GLUT4 plasma membrane fusion and subsequent glucose uptake and increasing intracellular Ca(2+) through the G protein-PLC-IP(3)-IP(3)R pathway. Treatment with 0 mM extracellular Ca(2+) + Ca(2+) chelator did not inhibit neferine-induced GLUT4 expression but blocked neferine-induced GLUT4 plasma membrane fusion and glucose uptake, suggesting the latter two are Ca(2+)-dependent. Therefore, we conclude that neferine is a potential treatment for type 2 diabetes. Frontiers Media S.A. 2019-09-04 /pmc/articles/PMC6737894/ /pubmed/31551792 http://dx.doi.org/10.3389/fphar.2019.00999 Text en Copyright © 2019 Zhao, Tian, Song, Ming, Liu, Shen, Liu and Yang http://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 Zhao, Ping Tian, Di Song, Guanjun Ming, Qian Liu, Jia Shen, Jinhua Liu, Qing-Hua Yang, Xinzhou Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells |
title | Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells |
title_full | Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells |
title_fullStr | Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells |
title_full_unstemmed | Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells |
title_short | Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells |
title_sort | neferine promotes glut4 expression and fusion with the plasma membrane to induce glucose uptake in l6 cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737894/ https://www.ncbi.nlm.nih.gov/pubmed/31551792 http://dx.doi.org/10.3389/fphar.2019.00999 |
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