Adiponectin receptor 1-mediated micro RNA-323-3p regulates functions of the MIN6 cell line via the AMP-activated protein kinase/sirtuin-1 pathway

J Int Med Res. 2018 May;46(5):1693-1708. doi: 10.1177/0300060518758584. Epub 2018 Mar 7.

Abstract

Background The development of an effective treatment for type 2 diabetes mellitus is urgently needed. This study aimed to investigate the role of micro RNA (miR)-323-3p in regulating the expression of adiponectin receptor 1 (AdipoR1), as well as the insulin secretion and cell function of pancreatic MIN6 β-cells. Methods MIN6 cells were treated with miR-323-3p mimics or inhibitors, and the effects on cell growth, proliferation, mitosis, and insulin secretion were studied. The expression levels of sirtuin-1 (SIRT-1) and AMP-activated protein kinase (AMPK) genes were also assessed. Results miR-323-3p directly targeted AdipoR1, and suppressed its expression at mRNA and protein levels. It also regulated the protein expression of SIRT-1 and AMPK, which are downstream target genes of the AdipoR1 signaling pathway. miR-323-3p suppressed cell growth, proliferation, mitosis, and insulin secretion of MIN6 cells. Conclusions miR-323-3p appears to be a crucial diabetes factor that mediates its functions by inhibiting the AdipoR1/AMPK/SIRT-1 signaling pathway. Our findings suggest that targeting AdipoR1 with inhibitors of miR-323-3p is a potential approach to improve the function of islet cells.

Keywords: MIN6 cell line; adiponectin receptor 1; diabetes mellitus; glucose metabolism; microRNA; sirtuin-1.

MeSH terms

  • 3' Untranslated Regions / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitosis / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism*
  • Signal Transduction* / drug effects
  • Sirtuin 1 / metabolism*

Substances

  • 3' Untranslated Regions
  • Insulin
  • MIRN323 microRNA, mouse
  • MicroRNAs
  • RNA, Messenger
  • Receptors, Adiponectin
  • AMP-Activated Protein Kinases
  • Sirtuin 1
  • Glucose