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J Cell Biochem. 2018 Oct 28; doi: 10.1002/jcb.27381. Epub 2018 Oct 28.

Network of three specific microRNAs influence type 2 diabetes through inducing insulin resistance in muscle cell lines.

Journal of cellular biochemistry

Maryam Honardoost, Farid Keramati, Ehsan Arefian, Samira Mohammadi Yeganeh, Masoud Soleimani

Affiliations

  1. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
  2. Department of Molecular Biology and Genetic Engineering, Stem Cell Technology Research Center, Tehran, Iran.
  3. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
  4. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  5. Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

PMID: 30368872 DOI: 10.1002/jcb.27381

Abstract

Insulin resistance has been implicated as one of the best predictors for type 2 diabetes. Growing evidence propose the involvement of microRNAs (miRNAs) as short regulatory molecules in modulating and inducing resistance. In this regard, we have investigated the role of three selected miRNAs in insulin resistance development (miR-135, miR-202, and miR-214), via assessing glucose uptake levels in C2C12 and L6 muscle cell lines. Interestingly, miRNA-transfected cells demonstrated a significantly different glucose uptake compared to the positive control cells. In addition, we evaluated the expression levels of three putative miRNA target genes (Rho-associated coiled-coil containing protein kinase 1, serine/threonine kinase 2, and vesicle-associated membrane protein 2) in transfected cells, recruiting luciferase assay. Our results indicated the targeting and downregulation of Rho-associated coiled-coil containing protein kinase 1 and serine/threonine kinase 2 genes in all miR-transfected cell lines ( P ≤ 0.05), but not for vesicle-associated membrane protein 2. MiRNA upregulation led to the poor stimulation of glucose uptake through insulin and developed insulin-resistant phenotype in both muscle cell lines. Our study showed the role of three miRNAs in the induction of insulin resistance in cell lines and making them prone to type 2 diabetes development.

© 2018 Wiley Periodicals, Inc.

Keywords: insulin resitance; miR-135; miR-202; miR-214; type 2 diabetes

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