Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Jing, Lv, Yuncheng, Zhao, Zhibo, Li, Wu, Xiang, Sunmin, Zhou, Lingzhi, Gao, Anbo, Yan, Bin, Ou, Lingling, Ling, Hong, Xiao, Xinhua, Liu, Jianghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
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
_version_ 1783431816573616128
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
work_keys_str_mv AT yangjing amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT lvyuncheng amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT zhaozhibo amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT liwu amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT xiangsunmin amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT zhoulingzhi amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT gaoanbo amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT yanbin amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT oulingling amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT linghong amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT xiaoxinhua amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT liujianghua amicrorna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT yangjing microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT lvyuncheng microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT zhaozhibo microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT liwu microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT xiangsunmin microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT zhoulingzhi microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT gaoanbo microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT yanbin microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT oulingling microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT linghong microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT xiaoxinhua microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion
AT liujianghua microrna24tosecretagoginregulatorypathwaymediatescholesterolinducedinhibitionofinsulinsecretion