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A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion
Hypercholesterolemia is a key factor leading to β-cell dysfunction, but its underlying mechanisms remain unclear. Secretagogin (Scgn), a Ca(2+) sensor protein that is expressed at high levels in the islets, has been shown to play a key role in regulating insulin secretion through effects on the solu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605698/ https://www.ncbi.nlm.nih.gov/pubmed/31173188 http://dx.doi.org/10.3892/ijmm.2019.4224 |
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author | Yang, Jing Lv, Yuncheng Zhao, Zhibo Li, Wu Xiang, Sunmin Zhou, Lingzhi Gao, Anbo Yan, Bin Ou, Lingling Ling, Hong Xiao, Xinhua Liu, Jianghua |
author_facet | Yang, Jing Lv, Yuncheng Zhao, Zhibo Li, Wu Xiang, Sunmin Zhou, Lingzhi Gao, Anbo Yan, Bin Ou, Lingling Ling, Hong Xiao, Xinhua Liu, Jianghua |
author_sort | Yang, Jing |
collection | PubMed |
description | Hypercholesterolemia is a key factor leading to β-cell dysfunction, but its underlying mechanisms remain unclear. Secretagogin (Scgn), a Ca(2+) sensor protein that is expressed at high levels in the islets, has been shown to play a key role in regulating insulin secretion through effects on the soluble N-ethylmaleimide-sensitive factor attachment receptor protein complexes. However, further studies are required to determine whether Scgn plays a role in hypercholesterolemia-associated β-cell dysfunction. The present study investigated the involvement of a microRNA-24 (miR-24)-to-Scgn regulatory pathway in cholesterol-induced β-cell dysfunction. In the present study, MIN6 cells were treated with increasing concentrations of cholesterol and then, the cellular functions and changes in the miR-24-to-Scgn signal pathway were observed. Excessive uptake of cholesterol in MIN6 cells increased the expression of miR-24, resulting in a reduction in Sp1 expression by directly targeting its 3′ untranslated region. As a transcriptional activator of Scgn, downregulation of Sp1 decreased Scgn levels and subsequently decreased the phosphorylation of focal adhesion kinase and paxillin, which is regulated by Scgn. Therefore, the focal adhesions in insulin granules were impaired and insulin exocytosis was reduced. The present study concluded that a miR-24-to-Scgn pathway participates in the mechanism regulating cholesterol accumulation-induced β-cell dysfunction. |
format | Online Article Text |
id | pubmed-6605698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-66056982019-07-29 A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion Yang, Jing Lv, Yuncheng Zhao, Zhibo Li, Wu Xiang, Sunmin Zhou, Lingzhi Gao, Anbo Yan, Bin Ou, Lingling Ling, Hong Xiao, Xinhua Liu, Jianghua Int J Mol Med Articles Hypercholesterolemia is a key factor leading to β-cell dysfunction, but its underlying mechanisms remain unclear. Secretagogin (Scgn), a Ca(2+) sensor protein that is expressed at high levels in the islets, has been shown to play a key role in regulating insulin secretion through effects on the soluble N-ethylmaleimide-sensitive factor attachment receptor protein complexes. However, further studies are required to determine whether Scgn plays a role in hypercholesterolemia-associated β-cell dysfunction. The present study investigated the involvement of a microRNA-24 (miR-24)-to-Scgn regulatory pathway in cholesterol-induced β-cell dysfunction. In the present study, MIN6 cells were treated with increasing concentrations of cholesterol and then, the cellular functions and changes in the miR-24-to-Scgn signal pathway were observed. Excessive uptake of cholesterol in MIN6 cells increased the expression of miR-24, resulting in a reduction in Sp1 expression by directly targeting its 3′ untranslated region. As a transcriptional activator of Scgn, downregulation of Sp1 decreased Scgn levels and subsequently decreased the phosphorylation of focal adhesion kinase and paxillin, which is regulated by Scgn. Therefore, the focal adhesions in insulin granules were impaired and insulin exocytosis was reduced. The present study concluded that a miR-24-to-Scgn pathway participates in the mechanism regulating cholesterol accumulation-induced β-cell dysfunction. D.A. Spandidos 2019-08 2019-05-31 /pmc/articles/PMC6605698/ /pubmed/31173188 http://dx.doi.org/10.3892/ijmm.2019.4224 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Yang, Jing Lv, Yuncheng Zhao, Zhibo Li, Wu Xiang, Sunmin Zhou, Lingzhi Gao, Anbo Yan, Bin Ou, Lingling Ling, Hong Xiao, Xinhua Liu, Jianghua A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
title | A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
title_full | A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
title_fullStr | A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
title_full_unstemmed | A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
title_short | A microRNA-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
title_sort | microrna-24-to-secretagogin regulatory pathway mediates cholesterol-induced inhibition of insulin secretion |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605698/ https://www.ncbi.nlm.nih.gov/pubmed/31173188 http://dx.doi.org/10.3892/ijmm.2019.4224 |
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