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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
  • View Affiliations / Copyright

    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
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 608-616
    |
    Published online on: May 31, 2019
       https://doi.org/10.3892/ijmm.2019.4224
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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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1 

Brunham LR, Kruit JK, Verchere CB and Hayden MR: Cholesterol in islet dysfunction and type 2 diabetes. J Clin Invest. 118:403–408. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Hao M, Head WS, Gunawardana SC, Hasty AH and Piston DW: Direct effect of cholesterol on insulin secretion: A novel mechanism for pancreatic beta-cell dysfunction. Diabetes. 56:2328–2338. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Xu Y, Toomre DK, Bogan JS and Hao M: Excess cholesterol inhibits glucose-stimulated fusion pore dynamics in insulin exocytosis. J Cell Mol Med. 21:2950–2962. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Bogan JS, Xu Y and Hao M: Cholesterol accumulation increases insulin granule size and impairs membrane trafficking. Traffic. 13:1466–1480. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Kruit JK, Kremer PH, Dai L, Tang R, Ruddle P, de Haan W, Brunham LR, Verchere CB and Hayden MR: Cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) and cholesterol uptake via the LDL receptor influences cholesterol-induced impairment of beta cell function in mice. Diabetologia. 53:1110–1119. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P and Stoffel M: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432:226–230. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Osmai M, Osmai Y, Bang-Berthelsen CH, Pallesen EM, Vestergaard AL, Novotny GW, Pociot F and Mandrup-Poulsen T: MicroRNAs as regulators of beta-cell function and dysfunction. Diabetes Metab Res Rev. 32:334–349. 2016. View Article : Google Scholar

8 

Li Y, Luo T, Wang L, Wu J and Guo S: MicroRNA-19a-3p enhances the proliferation and insulin secretion, while it inhibits the apoptosis of pancreatic cells via the inhibition of SOCS3. Int J Mol Med. 38:1515–1524. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Tugay K, Guay C, Marques AC, Allagnat F, Locke JM, Harries LW, Rutter GA and Regazzi R: Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets. Diabetologia. 59:161–169. 2016. View Article : Google Scholar

10 

Zhu Y, You W, Wang H, Li Y, Qiao N, Shi Y, Zhang C, Bleich D and Han X: MicroRNA-24/MODY gene regulatory pathway mediates pancreatic beta-cell dysfunction. Diabetes. 62:3194–3206. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Malenczyk K, Girach F, Szodorai E, Storm P, Segerstolpe A, Tortoriello G, Schnell R, Mulder J, Romanov RA, Borok E, et al: A TRPV1-to-secretagogin regulatory axis controls pancreatic beta-cell survival by modulating protein turnover. EMBO J. 36:2107–2125. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Wagner L, Oliyarnyk O, Gartner W, Nowotny P, Groeger M, Kaserer K, Waldhausl W and Pasternack MS: Cloning and expression of secretagogin, a novel neuroendocrine- and pancreatic islet of langerhans-specific Ca2+-binding protein. J Biol Chem. 275:24740–24751. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Yang SY, Lee JJ, Lee JH, Lee K, Oh SH, Lim YM, Lee MS and Lee KJ: Secretagogin affects insulin secretion in pancreatic beta-cells by regulating actin dynamics and focal adhesion. Biochem J. 473:1791–1803. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

15 

Lv YC, Tang YY, Peng J, Zhao GJ, Yang J, Yao F, Ouyang XP, He PP, Xie W, Tan YL, et al: MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1. Atherosclerosis. 236:215–226. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Staaf J, Ubhayasekera SJ, Sargsyan E, Chowdhury A, Kristinsson H, Manell H, Bergquist J, Forslund A and Bergsten P: Initial hyperinsulinemia and subsequent beta-cell dysfunction is associated with elevated palmitate levels. Pediatr Res. 80:267–274. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Barlow J, Jensen VH, Jastroch M and Affourtit C: Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets. Biochem J. 473:487–496. 2016. View Article : Google Scholar

18 

Tiwari J, Gupta G, de Jesus Andreoli Pinto T, Sharma R, Pabreja K, Matta Y, Arora N, Mishra A, Sharma R and Dua K: Role of microRNAs (miRNAs) in the pathophysiology of diabetes mellitus. Panminerva Med. 60:25–28. 2018.

19 

Hashimoto N and Tanaka T: Role of miRNAs in the pathogenesis and susceptibility of diabetes mellitus. J Hum Genet. 62:141–150. 2017. View Article : Google Scholar

20 

Calderari S, Diawara MR, Garaud A and Gauguier D: Biological roles of microRNAs in the control of insulin secretion and action. Physiol Genomics. 49:1–10. 2017. View Article : Google Scholar

21 

Gu C, Stein GH, Pan N, Goebbels S, Hornberg H, Nave KA, Herrera P, White P, Kaestner KH, Sussel L and Lee JE: Pancreatic beta cells require NeuroD to achieve and maintain functional maturity. Cell Metab. 11:298–310. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Zhang ZW, Zhang LQ, Ding L, Wang F, Sun YJ, An Y, Zhao Y, Li YH and Teng CB: MicroRNA-19b downregulates insulin 1 through targeting transcription factor neuroD1. FEBS Lett. 585:2592–2598. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Lee JJ, Yang SY, Park J, Ferrell JE Jr, Shin DH and Lee KJ: Calcium ion induced structural changes promote dimerization of secretagogin, which is required for its insulin secretory function. Sci Rep. 7:69762017. View Article : Google Scholar : PubMed/NCBI

24 

Kobayashi M, Yamato E, Tanabe K, Tashiro F, Miyazaki S and Miyazaki J: Functional analysis of novel candidate regulators of insulin secretion in the MIN6 mouse pancreatic beta cell line. PLoS One. 11:e01519272016. View Article : Google Scholar

25 

Bazwinsky-Wutschke I, Wolgast S, Muhlbauer E and Peschke E: Distribution patterns of calcium-binding proteins in pancreatic tissue of non-diabetic as well as type 2 diabetic rats and in rat insulinoma beta-cells (INS-1). Histochem Cell Biol. 134:115–127. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Segerstolpe A, Palasantza A, Eliasson P, Andersson EM, Andreasson AC, Sun X, Picelli S, Sabirsh A, Clausen M, Bjursell MK, et al: Single-cell transcriptome profiling of human pancreatic islets in health and Type 2 diabetes. Cell Metabo. 24:593–607. 2016. View Article : Google Scholar

27 

Hansson SF, Zhou AX, Vachet P, Eriksson JW, Pereira MJ, Skrtic S, Jongsm Wallin H, Ericsson-Dahistrand A, Karlsson D, Ahnmark A, et al: Secretagogin is increased in plasma from type 2 diabetes patients and potentially reflects stress and islet dysfunction. PLoS One. 13:e01966012018. View Article : Google Scholar : PubMed/NCBI

28 

Rorsman P and Renstrom E: Insulin granule dynamics in pancreatic beta cells. Diabetologia. 46:1029–1045. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Heaslip AT, Nelson SR, Lombardo AT, Beck Previs S, Armstrong J and Warshaw DM: Cytoskeletal dependence of insulin granule movement dynamics in INS-1 beta-cells in response to glucose. PLoS One. 9. pp. e1090822014, View Article : Google Scholar

30 

Rondas D, Tomas A and Halban PA: Focal adhesion remodeling is crucial for glucose-stimulated insulin secretion and involves activation of focal adhesion kinase and paxillin. Diabetes. 60:1146–1157. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang J, Lv Y, Zhao Z, Li W, Xiang S, Zhou L, Gao A, Yan B, Ou L, Ling H, Ling H, et al: A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion. Int J Mol Med 44: 608-616, 2019.
APA
Yang, J., Lv, Y., Zhao, Z., Li, W., Xiang, S., Zhou, L. ... Liu, J. (2019). A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion. International Journal of Molecular Medicine, 44, 608-616. https://doi.org/10.3892/ijmm.2019.4224
MLA
Yang, J., Lv, Y., Zhao, Z., Li, W., Xiang, S., Zhou, L., Gao, A., Yan, B., Ou, L., Ling, H., Xiao, X., Liu, J."A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion". International Journal of Molecular Medicine 44.2 (2019): 608-616.
Chicago
Yang, J., Lv, Y., Zhao, Z., Li, W., Xiang, S., Zhou, L., Gao, A., Yan, B., Ou, L., Ling, H., Xiao, X., Liu, J."A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion". International Journal of Molecular Medicine 44, no. 2 (2019): 608-616. https://doi.org/10.3892/ijmm.2019.4224
Copy and paste a formatted citation
x
Spandidos Publications style
Yang J, Lv Y, Zhao Z, Li W, Xiang S, Zhou L, Gao A, Yan B, Ou L, Ling H, Ling H, et al: A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion. Int J Mol Med 44: 608-616, 2019.
APA
Yang, J., Lv, Y., Zhao, Z., Li, W., Xiang, S., Zhou, L. ... Liu, J. (2019). A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion. International Journal of Molecular Medicine, 44, 608-616. https://doi.org/10.3892/ijmm.2019.4224
MLA
Yang, J., Lv, Y., Zhao, Z., Li, W., Xiang, S., Zhou, L., Gao, A., Yan, B., Ou, L., Ling, H., Xiao, X., Liu, J."A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion". International Journal of Molecular Medicine 44.2 (2019): 608-616.
Chicago
Yang, J., Lv, Y., Zhao, Z., Li, W., Xiang, S., Zhou, L., Gao, A., Yan, B., Ou, L., Ling, H., Xiao, X., Liu, J."A microRNA‑24‑to‑secretagogin regulatory pathway mediates cholesterol‑induced inhibition of insulin secretion". International Journal of Molecular Medicine 44, no. 2 (2019): 608-616. https://doi.org/10.3892/ijmm.2019.4224
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