Studies on the development and functions of beta cells represent important areas in both Type 1 and 2 diabetes. We have made important advances in both the clinical and basic science arenas. Highlights include the following.
- ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis by DRC member Sander and others in Cell Reports (2016). Sander and colleagues employed time-lapse microscopy and fluorescent labeling of cells to show that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; dependent on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. Thus, regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis.
- The IRE1α/XBP1s Pathway Is Essential for the Glucose Response and Protection of β Cells, by DRC member Kaufman and others in PLOS Biology (2015). Kaufman and colleagues demonstrate that glucose activates the unfolded protein response transducer inositol-requiring enzyme 1 α (IRE1α) to initiate Xbp1 mRNA splicing in adult primary beta cells. Beta cell failure upon Ire1α deletion was primarily due to reduced proinsulin mRNA revealing that glucose activates IRE1α-mediated Xbp1 splicing to expand the secretory capacity of the beta cell for increased proinsulin synthesis and to limit oxidative stress that leads to beta cell failure.
- ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells by DRC member Evans and others in Cell Metabolism (2016). Evans and colleagues identify estrogen-related receptor α (ERRα) expression as a hallmark of adult, but not neonatal beta cells. Forced expression of ERRα in iPSC-derived β-like cells enables glucose-responsive secretion of human insulin, obviating in vivo maturation to achieve functionality, and offering a scalable approach for in vitro generation of functional human beta cells.