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Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway

BACKGROUND: Type 2 diabetes (T2D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance, resulting in an increase in blood glucose. However, the mechanism involved in this lack of insulin secretion is unclear. The level of vascular en...

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Autores principales: Jia, Jing-Dan, Jiang, Wen-Guo, Luo, Xu, Li, Rong-Rong, Zhao, Yu-Chi, Tian, Geng, Li, Ya-Na
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040075/
https://www.ncbi.nlm.nih.gov/pubmed/33889292
http://dx.doi.org/10.4239/wjd.v12.i4.480
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author Jia, Jing-Dan
Jiang, Wen-Guo
Luo, Xu
Li, Rong-Rong
Zhao, Yu-Chi
Tian, Geng
Li, Ya-Na
author_facet Jia, Jing-Dan
Jiang, Wen-Guo
Luo, Xu
Li, Rong-Rong
Zhao, Yu-Chi
Tian, Geng
Li, Ya-Na
author_sort Jia, Jing-Dan
collection PubMed
description BACKGROUND: Type 2 diabetes (T2D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance, resulting in an increase in blood glucose. However, the mechanism involved in this lack of insulin secretion is unclear. The level of vascular endothelial growth factor B (VEGF-B) is significantly increased in T2D patients. The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation. It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin. As an in vitro model of normal pancreatic β-cells, the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects. AIM: To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation. METHODS: The MIN6 mouse pancreatic islet β-cell line was used as the model system. By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells, we examined the effects of VEGF-B on insulin secretion, Ca(2+) and cyclic adenosine monophosphate (cAMP) levels, and the insulin secretion signaling pathway. RESULTS: Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca(2+) and cAMP in MIN6 cells. Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1 (PLCγ1), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase (AKT), and other proteins in the insulin secretion pathway. Upon knockdown of VEGF-B, MIN6 cells exhibited increased insulin secretion and Ca(2+) and cAMP levels and upregulated expression of PLCγ1, PI3K, AKT, and other proteins. CONCLUSION: VEGF-B can regulate insulin secretion by modulating the levels of Ca(2+) and cAMP. VEGF-B involvement in insulin secretion is related to the expression of PLCγ1, PI3K, AKT, and other signaling proteins. These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2D.
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spelling pubmed-80400752021-04-21 Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway Jia, Jing-Dan Jiang, Wen-Guo Luo, Xu Li, Rong-Rong Zhao, Yu-Chi Tian, Geng Li, Ya-Na World J Diabetes Basic Study BACKGROUND: Type 2 diabetes (T2D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance, resulting in an increase in blood glucose. However, the mechanism involved in this lack of insulin secretion is unclear. The level of vascular endothelial growth factor B (VEGF-B) is significantly increased in T2D patients. The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation. It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin. As an in vitro model of normal pancreatic β-cells, the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects. AIM: To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation. METHODS: The MIN6 mouse pancreatic islet β-cell line was used as the model system. By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells, we examined the effects of VEGF-B on insulin secretion, Ca(2+) and cyclic adenosine monophosphate (cAMP) levels, and the insulin secretion signaling pathway. RESULTS: Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca(2+) and cAMP in MIN6 cells. Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1 (PLCγ1), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase (AKT), and other proteins in the insulin secretion pathway. Upon knockdown of VEGF-B, MIN6 cells exhibited increased insulin secretion and Ca(2+) and cAMP levels and upregulated expression of PLCγ1, PI3K, AKT, and other proteins. CONCLUSION: VEGF-B can regulate insulin secretion by modulating the levels of Ca(2+) and cAMP. VEGF-B involvement in insulin secretion is related to the expression of PLCγ1, PI3K, AKT, and other signaling proteins. These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2D. Baishideng Publishing Group Inc 2021-04-15 2021-04-15 /pmc/articles/PMC8040075/ /pubmed/33889292 http://dx.doi.org/10.4239/wjd.v12.i4.480 Text en ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Basic Study
Jia, Jing-Dan
Jiang, Wen-Guo
Luo, Xu
Li, Rong-Rong
Zhao, Yu-Chi
Tian, Geng
Li, Ya-Na
Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway
title Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway
title_full Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway
title_fullStr Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway
title_full_unstemmed Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway
title_short Vascular endothelial growth factor B inhibits insulin secretion in MIN6 cells and reduces Ca(2+) and cyclic adenosine monophosphate levels through PI3K/AKT pathway
title_sort vascular endothelial growth factor b inhibits insulin secretion in min6 cells and reduces ca(2+) and cyclic adenosine monophosphate levels through pi3k/akt pathway
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040075/
https://www.ncbi.nlm.nih.gov/pubmed/33889292
http://dx.doi.org/10.4239/wjd.v12.i4.480
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