miR‑6835‑3p regulates the function of pancreatic islet cells by modulating the expression of AdipoR1

Wang,Huimin; Jiang,Lei; Li,Zhenfu; Wang,Wei; Hao,Chuanji

doi:10.3892/ijmm.2018.3731

miR‑6835‑3p regulates the function of pancreatic islet cells by modulating the expression of AdipoR1

Authors:
- Huimin Wang
- Lei Jiang
- Zhenfu Li
- Wei Wang
- Chuanji Hao
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Affiliations: Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China, Department of Cardiac Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China
Published online on: June 15, 2018 https://doi.org/10.3892/ijmm.2018.3731
Pages: 1317-1326
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Effective drugs and strategies for treating type 2 diabetes mellitus (2‑DM) are urgently required. The aim of the present study was to elucidate the mechanism underlying microRNA (miR)‑6835‑3p regulation of adiponectin receptor 1 (AdipoR1) expression and the miR‑6835‑3p/AdipoR1 signaling pathway in pancreatic islet cells. In addition, the potential anti‑diabetes effect of miR‑6835‑3p on insulin secretion was investigated. Luciferase activity analysis was performed to evaluate how miR‑6835‑3p targets the 3'‑untranslated region of AdipoR1. The SU.86.86 and MIN‑6 cell lines were co‑cultured with or without miR‑6835‑3p inhibitors or mimics, and the insulin secretory functions of these cell lines were then determined. Luciferase reporter analysis revealed that AdipoR1 was a direct target of miR‑6835‑3p. In addition, miR‑6835‑3p overexpression suppressed the mRNA and protein expression levels of AdipoR1 in the SU.86.86 and MIN‑6 cell lines. Furthermore, miR‑6835‑3p exerted negative effects on insulin secretion in SU.86.86 and MIN‑6 cells, which were mediated by regulating AdipoR1 expression. AdipoR1 was a direct target of miR‑6835‑3p; therefore, inhibition of AdiopR1 expression may reduce insulin secretion and may be considered a key regulator of insulin secretion. The results of the present study suggested that targeting AdipoR1 with miR‑6835‑3p inhibitors may be a potential strategy for promoting glucose‑stimulated insulin secretion, and thereby, may be an effective treatment for type 2‑DM.

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1	Asif M: The prevention and control the type-2 diabetes by changing lifestyle and dietary pattern. J Educ Health Promot. 3:1–8. 2014. View Article : Google Scholar : PubMed/NCBI
2	Riobo Servan P: Obesity and diabetes. Nutr Hosp. 28:138–143. 2013.PubMed/NCBI
3	Xiao J, Chen T and Cao H: Flavonoid glycosylation and biological benefits. Biotechnol Adv. May 22–2014.Epub ahead of print. View Article : Google Scholar
4	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
5	Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F and Mobarra N: Pancreatic islet differentiation of human embryonic stem cells by microRNA overexpression. J Tissue Eng Regen Med. 10:527–534. 2016. View Article : Google Scholar
6	Stefani G and Slack FJ: Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 9:219–230. 2008. View Article : Google Scholar : PubMed/NCBI
7	Shi Y and Jin Y: MicroRNA in cell differentiation and development. Sci China C Life Sci. 52:205–211. 2009. View Article : Google Scholar : PubMed/NCBI
8	Carrington JC and Ambros V: Role of microRNAs in plant and animal development. Science. 301:336–338. 2003. View Article : Google Scholar : PubMed/NCBI
9	Kaviani M, Azarpira N, Karimi MH and Al-Abdullah I: The role of microRNAs in islet β-cell development. Cell Biol Int. 40:1248–1255. 2016. View Article : Google Scholar : PubMed/NCBI
10	Dalgaard LT and Eliasson L: An ‘alpha-beta’ of pancreatic islet microribonucleotides. Int J Biochem Cell Biol. 88:208–219. 2017. View Article : Google Scholar : PubMed/NCBI
11	Shewade YM, Umrani M and Bhonde RR: Large-scale isolation of islets by tissue culture of adult mouse pancreas. Transplant Proc. 31:1721–1723. 1999. View Article : Google Scholar : PubMed/NCBI
12	O’Connell RM, Taganov KD, Boldin MP, Cheng G and Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA. 104:1604–1609. 2007. View Article : Google Scholar
13	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. 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	Nikolai VK and Steve JU: Association of RNA polymerase complexes of the parasitic protozoan cryptosporidium parvum with virus-like particles: Heterogeneous system. J Virol. 74:5788–5795. 2000. View Article : Google Scholar
16	Sebastiani G, Po A, Miele E, Ventriglia G, Ceccarelli E, Bugliani M, Marselli L, Marchetti P, Gulino A, Ferretti E and Dotta F: MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion. Acta Diabetol. 52:523–530. 2015. View Article : Google Scholar
17	da Silva Xavier G, Loder MK, McDonald A, Tarasov AI, Carzaniga R, Kronenberger K, Barg S and Rutter GA: TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes. 58:894–905. 2009. View Article : Google Scholar : PubMed/NCBI
18	Weir GC and Bonner-Weir S: Sleeping islets and the relationship between β-cell mass and function. Diabetes. 60:2018–2019. 2011. View Article : Google Scholar : PubMed/NCBI
19	Kahn SE: The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 46:3–19. 2003. View Article : Google Scholar : PubMed/NCBI
20	Maris M, Ferreira GB, D’Hertog W, Cnop M, Waelkens E, Overbergh L and Mathieu C: High glucose induces dysfunction in insulin secretory cells by different pathways: A proteomic approach. J Proteome Res. 9:6274–6287. 2010. View Article : Google Scholar : PubMed/NCBI
21	Locke JM, da Silva Xavier G, Dawe HR, Rutter GA and Harries LW: Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion. Diabetologia. 57:122–128. 2014. View Article : Google Scholar
22	Ramachandran D, Roy U, Garg S, Ghosh S, Pathak S and Kolthur-Seetharam U: Sirt1 and mir-9 expression is regulated during glucose-stimulated insulin secretion in pancreatic β-islets. FEBS J. 278:1167–1174. 2011. View Article : Google Scholar : PubMed/NCBI
23	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. 2015. View Article : Google Scholar : PubMed/NCBI
24	Thirone AC, Huang C and Klip A: Tissue-specific roles of IRS proteins in insulin signaling and glucose transport. Trends Endocrinol Metab. 17:72–78. 2006. View Article : Google Scholar : PubMed/NCBI
25	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
26	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
27	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
28	Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, Rutter GA and Van Obberghen E: MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem. 282:19575–19588. 2007. View Article : Google Scholar : PubMed/NCBI
29	Hu S, Wang H, Chen K, Cheng P, Gao S, Liu J, Li X and Sun X: MicroRNA-34c downregulation ameliorates-amyloid-β-induced synaptic failure and memory deficits by targeting VAMP2. J Alzheimers Dis. 48:673–686. 2015. View Article : Google Scholar
30	Fisman EZ and Tenenbaum A: Adiponectin: A manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease. Cardiovasc Diabetol. 13:1032014. View Article : Google Scholar
31	Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, et al: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 423:762–769. 2003. View Article : Google Scholar : PubMed/NCBI
32	Yamauchi T, Iwabu M, Okada-Iwabu M and Kadowaki T: Adiponectin receptors: A review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 28:15–23. 2014. View Article : Google Scholar : PubMed/NCBI
33	Park HS, Lim JH, Kim MY, Kim Y, Hong YA, Choi SR, Chung S, Kim HW, Choi BS, Kim YS, et al: Resveratrol increases AdipoR1 and AdipoR2 expression in type 2 diabetic nephropathy. J Transl Med. 14:1762016. View Article : Google Scholar : PubMed/NCBI
34	Pramanik KC, Fofaria NM, Gupta P and Srivastava SK: CBP-mediated FOXO-1 acetylation inhibits pancreatic tumor growth by targeting SirtT. Mol Cancer Ther. 13:687–698. 2014. View Article : Google Scholar : PubMed/NCBI