Open Access

Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus

  • Authors:
    • Yitao Chen
    • Yangsheng Wu
    • Yuanxiao Yang
    • Zhiwei Xu
    • Junfeng Tong
    • Zheming Li
    • Xiaojie Zhou
    • Changyu Li
  • View Affiliations

  • Published online on: March 6, 2018     https://doi.org/10.3892/ijmm.2018.3535
  • Pages: 3327-3341
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The main actions of metformin are as follows: To reduce hyperglycemia via the suppression of gluconeogenesis, improve glucose uptake and insulin sensitivity, and stimulate activation of adenosine monophosphate‑activated protein kinase during the treatment of diabetes mellitus. It is well known that metformin acts via complex mechanisms, including multitarget and multipathway mechanisms; however, the multitargeted antidiabetic genes of metformin remain obscure. The present study aimed to perform transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus. The type 2 diabetes rat model was established using streptozotocin. Fasting blood glucose, hemoglobin A1c, serum insulin and biological parameters were subsequently measured. Differentially expressed genes (DEGs) and proteins were identified in the rat livers by expression profile analysis and isobaric tags for relative and absolute quantitation (iTRAQ). A 1.5‑fold alteration in gene expression, as determined using chip‑based expression profile analysis, and a 1.2‑fold alteration in protein expression, as determined using iTRAQ, were considered physiologically significant benchmarks, which were used to identify DEGS in metformin‑treated rats with type 2 diabetes mellitus. The DEGs were verified using quantitative polymerase chain reaction (qPCR) and western blot analysis. Numerous hepatic genes involved in various metabolic pathways were affected by metformin; in particular, genes associated with lipid metabolism were markedly affected. Expression profile analysis and iTRAQ analysis suggested that carboxylesterase 1C subunit (Ces1C) and cholesterol 7α‑hydroxylyase (Cyp7a1) may serve as important DEGs, which were validated by qPCR and western blot analysis. Ces1C and Cyp7a1 are the main enzymes in cholesterol metabolism, yet the result of western blotting was not consistent with qPCR. The present study demonstrated that metformin may affect the expression of numerous hepatic genes involved in metabolic pathways, particularly the lipid and cholesterol metabolic pathways. Ces1C and Cyp7a1 may be considered novel therapeutic target genes in the liver, which are involved in the antidiabetic effects of metformin.
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June-2018
Volume 41 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chen Y, Wu Y, Yang Y, Xu Z, Tong J, Li Z, Zhou X and Li C: Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus. Int J Mol Med 41: 3327-3341, 2018
APA
Chen, Y., Wu, Y., Yang, Y., Xu, Z., Tong, J., Li, Z. ... Li, C. (2018). Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus. International Journal of Molecular Medicine, 41, 3327-3341. https://doi.org/10.3892/ijmm.2018.3535
MLA
Chen, Y., Wu, Y., Yang, Y., Xu, Z., Tong, J., Li, Z., Zhou, X., Li, C."Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus". International Journal of Molecular Medicine 41.6 (2018): 3327-3341.
Chicago
Chen, Y., Wu, Y., Yang, Y., Xu, Z., Tong, J., Li, Z., Zhou, X., Li, C."Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformin‑treated Sprague‑Dawley rats with type 2 diabetes mellitus". International Journal of Molecular Medicine 41, no. 6 (2018): 3327-3341. https://doi.org/10.3892/ijmm.2018.3535