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

doi:10.3892/ijmm.2019.4224

A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion

Authors:
- Jing Yang
- Yuncheng Lv
- Zhibo Zhao
- Wu Li
- Sunmin Xiang
- Lingzhi Zhou
- Anbo Gao
- Bin Yan
- Lingling Ou
- Hong Ling
- Xinhua Xiao
- Jianghua Liu
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Affiliations: Department of Endocrinology, The First Affiliated Hospital of The University of South China, Hengyang, Hunan 421001, P.R. China, Laboratory of Clinical Anatomy and Reproductive Medicine, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Paediatrics, The First Affiliated Hospital of The University of South China, Hengyang, Hunan 421001, P.R. China, Emergency Surgery, The First Affiliated Hospital of The University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: May 31, 2019 https://doi.org/10.3892/ijmm.2019.4224
Pages: 608-616
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypercholesterolemia is a key factor leading to β‑cell dysfunction, but its underlying mechanisms remain unclear. Secretagogin (Scgn), a Ca2+ 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.

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