Dataset Information
MiR-375 gene dosage in pancreatic ?-cells: implications for regulation of ?-cell mass and biomarker development.
Ontology highlight
ABSTRACT: Unlabelled
MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased ?-cell and increased ?-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal ?-cell mass and function. Selective re-expression of miR-375 in ?-cells of miR-375KO mice normalizes both, ?- and ?-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of ?-cells to the total plasma miR-375 levels. Only a small proportion (?1 %) of circulating miR-375 originates from ?-cells. Furthermore, acute and profound ?-cell destruction is sufficient to detect elevations of miR-375 levels in the blood. These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients. Together, our data support an essential role for miR-375 in the maintenance of ?-cell mass and provide in vivo evidence for release of miRNAs from pancreatic ?-cells. The small contribution of ?-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for ?-cell function but suggests a utility for the detection of acute ?-cell death for autoimmune diabetes.Key messages
• Overexpression of miR-375 in ?-cells does not influence ?-cell mass and function. • Increased ?-cell mass in miR-375KO arises secondarily to loss of miR-375 in ?-cells. • Only a small proportion of circulating miR-375 levels originates from ?-cells. • Acute ?-cell destruction results in measurable increases of miR-375 in the blood. Circulating miR-375 levels are not a biomarker for pancreatic ?-cell function.
SUBMITTER: Latreille M
PROVIDER: S-EPMC4589563 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
Publications
miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development.
Journal of molecular medicine (Berlin, Germany) 20150528 10
<h4>Unlabelled</h4>MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased β-cell and increased α-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal β-cell mass and function. Selective re-expression of miR-375 in β-cells of miR-375KO mice normalizes ...[more]