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

  1. Doris A. Stoffers1
  1. 1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
  2. 2Division of Transplant Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
  1. Corresponding author: Doris A. Stoffers, stoffers{at}mail.med.upenn.edu

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.

Footnotes

  • Received April 12, 2012.
  • Accepted September 22, 2012.

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  1. Diabetes vol. 62 no. 3 887-895
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