17 research outputs found
miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development
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 both, α- and β-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of β-cells to the total plasma miR-375 levels. Only a small proportion (≈1 %) of circulating miR-375 originates from β-cells. Furthermore, acute and profound β-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 β-cell mass and provide in vivo evidence for release of miRNAs from pancreatic β-cells. The small contribution of β-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for β-cell function but suggests a utility for the detection of acute β-cell death for autoimmune diabetes
Inhomogeneous ground state and the coexistence of two length scales near phase transitions in real solids
Real crystals almost unavoidably contain a finite density of dislocations. We
show that this generic type of long--range correlated disorder leads to a
breakdown of the conventional scenario of critical behavior and standard
renormalization group techniques based on the existence of a simple,
homogeneous ground state. This breakdown is due to the appearance of an
inhomogeneous ground state that changes the character of the phase transition
to that of a percolative phenomenon. This scenario leads to a natural
explanation for the appearance of two length scales in recent high resolution
small-angle scattering experiments near magnetic and structural phase
transitions.Comment: 4 pages, RevTex, no figures; also available from
http://www.tp3.ruhr-uni-bochum.de/archive/tpiii_archive.htm