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Article

Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion

  • Authors:
    • Xin Yu
    • Liyong Zhong
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, P.R. China
  • Pages: 7931-7938
    |
    Published online on: March 28, 2018
       https://doi.org/10.3892/mmr.2018.8813
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Abstract

MicroRNAs (miRs) are considered to be effective, post‑transcriptional regulators in the pathophysiology of type 2 diabetes (T2D) and promising treatment targets. However, the function of miR‑141 remains to be elucidated. In the present study, upregulation of miR‑141 was demonstrated in diabetic mice and elderly diabetic patients. Using reverse transcriptase‑quantitative polymerase chain reaction, luciferase reporter assays and western blotting, forkhead box A2 (FOXA2) was identified as a direct target gene of miR‑141. The potential role of miRNA‑141 or FOXA2 was evaluated by overexpressing or silencing miR‑141 or FOXA2, respectively. The increased expression of miR‑141 resulted in impaired glucose‑stimulated insulin secretion (GSIS) and INS‑1 β cell proliferation. In addition, miR‑141 silencing in MIN6 pseudoislets or INS‑1 β cells led to reduced T2D‑associated damage. Furthermore, the expression of miR‑141 may be corrected by treatment with pioglitazone, which is widely used for insulin resistance therapy. The present study also demonstrated the mechanism by which miR‑141 regulated GSIS and proliferation through FOXA2. Overexpression of FOXA2 in MIN6 pseudoislets increased the effect of the miR‑141 inhibitor on GSIS. FOXA2 effectively reversed the effect of miR‑141 overexpression on β cell proliferation. In conclusion, the results of the present study indicate that the pioglitazone/miR‑141/FOXA2 axis may represent a promising target mechanism for T2D treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Yu X and Zhong L: Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion. Mol Med Rep 17: 7931-7938, 2018.
APA
Yu, X., & Zhong, L. (2018). Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion. Molecular Medicine Reports, 17, 7931-7938. https://doi.org/10.3892/mmr.2018.8813
MLA
Yu, X., Zhong, L."Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion". Molecular Medicine Reports 17.6 (2018): 7931-7938.
Chicago
Yu, X., Zhong, L."Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion". Molecular Medicine Reports 17, no. 6 (2018): 7931-7938. https://doi.org/10.3892/mmr.2018.8813
Copy and paste a formatted citation
x
Spandidos Publications style
Yu X and Zhong L: Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion. Mol Med Rep 17: 7931-7938, 2018.
APA
Yu, X., & Zhong, L. (2018). Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion. Molecular Medicine Reports, 17, 7931-7938. https://doi.org/10.3892/mmr.2018.8813
MLA
Yu, X., Zhong, L."Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion". Molecular Medicine Reports 17.6 (2018): 7931-7938.
Chicago
Yu, X., Zhong, L."Pioglitazone/microRNA‑141/FOXA2: A novel axis in pancreatic β‑cells proliferation and insulin secretion". Molecular Medicine Reports 17, no. 6 (2018): 7931-7938. https://doi.org/10.3892/mmr.2018.8813
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