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Pancreatic beta cell proliferation has emerged as the principal mechanism for homeostatic maintenance of beta cell mass during adult life. This underscores the importance of understanding the mechanisms of beta cell replication and suggests novel approaches for regenerative therapy to treat diabetes. Here we use an in vivo pulse-chase labeling assay to(More)
Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report(More)
Most of our knowledge on cell kinetics stems from in vitro studies of continuously dividing cells. Here we determine in vivo cell cycle parameters of pancreatic beta-cells, a largely quiescent population, using drugs that mimic or prevent glucose-induced replication of beta-cells in mice. Quiescent beta-cells exposed to a mitogenic glucose stimulation(More)
The frequency of pancreatic β-cell replication declines dramatically with age, potentially contributing to the increased risk of type 2 diabetes in old age. Previous studies have shown the involvement of cell-autonomous factors in this phenomenon, particularly the decline of polycomb genes and accumulation of p16/INK4A. Here, we demonstrate that a systemic(More)
Although cysteine cathepsins have been identified as key regulators of cancer growth, their specific role in tumor development remains unclear. Recent studies have shown that high activity levels of tumor cathepsins are primarily a result of increased cathepsin activity in cancer-promoting tumor-associated macrophages (TAMs). To further investigate the role(More)
Both type 1 and type 2 diabetes patients would greatly benefit from transplantation of insulin-producing pancreatic beta cells; however, a severe shortage of transplantable beta cells is a major current limitation in the use of such therapy. Understanding the mechanisms by which beta cells are naturally formed is therefore a central challenge for modern(More)
The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those(More)
INTRODUCTION Discovery of enhanced glucose tolerance following bariatric surgery has sparked renewed interest in the investigation of unchartered underlying pathways of glucose homeostasis. Delineation of this pathway may ultimately be the first step in the creation of a novel therapy for type II diabetes. Nevertheless, the technical complexity and(More)
Activity-based probes are small molecules that can be used to monitor enzyme activity by covalently binding to specific residues in the active site. In this issue of Chemistry & Biology, Lu and colleagues developed a specific fluorescent activity-based probe that targets the papain-like cysteine bacterial type III effector protease AvrPphB and used it to(More)
AIMS/HYPOTHESIS Vascular endothelial growth factor (VEGF) has been recognised by loss-of-function experiments as a pleiotropic factor with importance in embryonic pancreas development and postnatal beta cell function. Chronic, nonconditional overexpression of VEGF-A has a deleterious effect on beta cell development and function. We report, for the first(More)