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
-
mTOR protein, mouse
-
TOR Serine-Threonine Kinases