Glucose-induced microRNA-17 promotes pancreatic beta cell proliferation through down-regulation of Menin

Eur Rev Med Pharmacol Sci. 2015 Feb;19(4):624-9.

Abstract

Objective: Menin, encoded by the Men1 gene, is responsible for β-cell tumor formation in patients with multiple endocrine neoplasia type 1. Recently, Menin has been proven to negatively regulate β-cell proliferation in several mouse models, including hyperglycemia. However, it is unclear how glucose regulates Menin expression in β-cells.

Materials and methods: In the present study, quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect the expression levels of MicroRNAs in Min-6 cells treated with high glucose, in which we found that miR-17 was significantly up-regulated.

Results: Further studies using bioinformatic prediction, luciferase and protein expression analysis suggested that miR-17 could inhibit protein levels of Menin through targeting its 3'-untranslated region.

Conclusions: Our results indicate that miR-17 might serve as an important intracellular target of glucose to mediate the mitogenic effect that glucose exerts in pancreatic β-cells.

MeSH terms

  • Animals
  • Cell Proliferation* / drug effects
  • Cell Proliferation* / genetics
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Female
  • Glucose / pharmacology*
  • Humans
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Multiple Endocrine Neoplasia Type 1 / complications
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Multiple Endocrine Neoplasia Type 1 / pathology
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation / drug effects

Substances

  • MEN1 protein, human
  • MIRN17 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Glucose