MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction

Yunxia Zhu, Weiyan You, Hongdong Wang, Yating Li, Nan Qiao, Yuguang Shi, Chenyu Zhang, David Bleich, Xiao Han

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Overnutrition and genetics both contribute separately to pancreatic β-cell dysfunction, but how these factors interact is unclear. This study was aimed at determining whether microRNAs (miRNAs) provide a link between these factors. In this study, miRNA-24 (miR-24) was highly expressed in pancreatic β-cells and further upregulated in islets from genetic fatty (db/db) or mice fed a high-fat diet, and islets subject to oxidative stress. Overexpression of miR-24 inhibited insulin secretion and β-cell proliferation, potentially involving 351 downregulated genes. By using bioinformatic analysis combined with luciferase-based promoter activity assays and quantitative real-time PCR assays, we identified two maturity-onset diabetes of the young (MODY) genes as direct targets of miR-24. Silencing either of these MODY genes (Hnf1a and Neurod1) mimicked the cellular phenotype caused by miR-24 overexpression, whereas restoring their expression rescued β-cell function. Our findings functionally link the miR-24/MODY gene regulatory pathway to the onset of type 2 diabetes and create a novel network between nutrient overload and genetic diabetes via miR-24.

Original languageEnglish (US)
Pages (from-to)3194-3206
Number of pages13
JournalDiabetes
Volume62
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

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Regulator Genes
MicroRNAs
Overnutrition
Genes
High Fat Diet
Mason-Type Diabetes
Computational Biology
Luciferases
Type 2 Diabetes Mellitus
Real-Time Polymerase Chain Reaction
Oxidative Stress
Down-Regulation
Cell Proliferation
Insulin
Phenotype
Food

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Zhu, Y., You, W., Wang, H., Li, Y., Qiao, N., Shi, Y., ... Han, X. (2013). MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction. Diabetes, 62(9), 3194-3206. https://doi.org/10.2337/db13-0151

MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction. / Zhu, Yunxia; You, Weiyan; Wang, Hongdong; Li, Yating; Qiao, Nan; Shi, Yuguang; Zhang, Chenyu; Bleich, David; Han, Xiao.

In: Diabetes, Vol. 62, No. 9, 01.09.2013, p. 3194-3206.

Research output: Contribution to journalArticle

Zhu, Y, You, W, Wang, H, Li, Y, Qiao, N, Shi, Y, Zhang, C, Bleich, D & Han, X 2013, 'MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction', Diabetes, vol. 62, no. 9, pp. 3194-3206. https://doi.org/10.2337/db13-0151
Zhu, Yunxia ; You, Weiyan ; Wang, Hongdong ; Li, Yating ; Qiao, Nan ; Shi, Yuguang ; Zhang, Chenyu ; Bleich, David ; Han, Xiao. / MicroRNA-24/MODY gene regulatory pathway mediates pancreatic β-cell dysfunction. In: Diabetes. 2013 ; Vol. 62, No. 9. pp. 3194-3206.
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