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

Second Order Phase Transition in Crystals with Long--Range Correlated Quenched Defects

We consider the phase transition in a ferromagnet with line defects that introduce a local variation of the critical temperature V (r) / r \Gamma\Delta ? , leading to a correlator hV (0)V (r)i / r \Gamma(2\Delta\Gammad) ? . We discuss conditions of both local and global character that lead to different scenarios for the transition, ranging from a "conventional" transition into a homogeneous phase that can be described within the framework of the standard Renormalization Group to a transition into an inhomogeneous phase with a percolating network of ordered regions. 64.60Ak Typeset using REVT E X I. INTRODUCTION There have been many investigations of the thermodynamic properties of crystals with quenched defects of the random temperature type near a second order phase transition point. 1 These defects can be described by an additional term H def = X k V d (r \Gamma r k )\Theta(r k ) j'(r)j 2 j V (r)j'(r)j 2 (1) in the Hamiltonian density. Here V d (r \Gamma r k ) is a si..