Citations

Abstract Context: Type 2 diabetes is characterized by a β-cell deficit and a progressive defect in β-cell function. It has been proposed that the deficit in β-cells may be due to β-cell degranulation and transdifferentiation to other endocrine cell types. Objective: The objective of the study was to establish the potential impact of β-cell dedifferentiation and transdifferentiation on β-cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated. Design, Setting, and Participants: Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases. Results: Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 ± 0.03 cells/islet vs 0.03 ± 0.01 cells/islet, P < .01), the impact on the β-cell deficit would be minimal. Furthermore, we established that the deficit in β-cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells. Conclusions: Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in β-cells in type 2 diabetes but may reflect, in part, attempted β-cell regeneration.

Filamin A (FLNA) is known to be involved in intracellular actin binding, cell migration, scaffolding, and signaling. We report a novel X‐linked syndrome characterized by cardiac valvular disease, keloid scarring and reduced joint mobility in male second cousins due to a previously unreported mutation in FLNA. Whole exome sequencing was performed using standard methods and segregation analysis was performed in affected and non‐affected family members. A novel hemizygous c.4726G>A (p.G1576R) mutation in FLNA was detected. Segregation analysis performed on multiple maternal family members showed c.4726G>A (p.G1576R) segregated with disease in an X‐linked inheritance pattern. The findings in these cases are distinct from previously described FLNA related disorders by virtue of decreased joint mobility and spontaneous keloid scarring. They occur in association with a novel mutation and represent a novel genetic syndrome. © 2015 Wiley Periodicals, Inc.