MicroRNA-7 Regulates the mTOR Pathway and Proliferation in Adult Pancreatic β-cells

Diabetes. 2013 Mar;62(3):887-95. doi: 10.2337/db12-0451. Epub 2012 Dec 6.

Abstract

Elucidating the mechanism underlying the poor proliferative capacity of adult pancreatic β-cells is critical to regenerative therapeutic approaches for diabetes. Here, we show that the microRNA (miR)-7/7ab family member miR-7a is enriched in mouse adult pancreatic islets compared with miR-7b. Remarkably, miR-7a targets five components of the mTOR signaling pathway. Further, inhibition of miR-7a activates mTOR signaling and promotes adult β-cell replication in mouse primary islets, which can be reversed by the treatment with a well-known mTOR inhibitor, rapamycin. These data suggest that miR-7 acts as a brake on adult β-cell proliferation. Most importantly, this miR-7-mTOR proliferation axis is conserved in primary human β-cells, implicating miR-7 as a therapeutic target for diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Molecular Targeted Therapy
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism*
  • Tissue Culture Techniques
  • Young Adult

Substances

  • Hypoglycemic Agents
  • MIRN7 microRNA, human
  • MIRN7 microRNA, mouse
  • MicroRNAs
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse