Foxm1b in endocrine pancreas growth and regeneration

β细胞质量是动态的，在生物体的整个生命过程中都会随着代谢变化和需求而变化。贝塔细胞质量的增加被认为是通过复制现有的贝塔细胞和从干细胞前体细胞新生的贝塔细胞来实现的。糖尿病是由绝对的(1型)或相对的(2型)功能不足的β细胞团引起的。因此，基因 而参与维持或改变β细胞质量的途径可能会对糖尿病患者产生影响。对这些基因的功能分析可能导致新的治疗策略，以增加糖尿病患者现有的β细胞质量和/或促进从胚胎或干细胞体外产生β细胞。Foxm1b转录因子在增殖细胞中高表达，激活细胞周期基因。肝脏特异性Foxm1b失活会损害肝部分切除后的肝再生。这些结果促使我们研究Foxm1b是否在胰腺和/或β细胞的再生和补偿中发挥类似的功能。我们发现Foxm1b在胚胎和新生儿的内分泌细胞中高表达，此时许多细胞处于增殖状态。使用Cre-lox策略，我们制作了胰腺特异的Foxm1b缺失的小鼠，以检查其在以下情况下胰腺再生中的作用 胰腺部分切除术。在整个胰腺中缺乏Foxm1b的小鼠在6岁时出现糖耐量异常 9周龄时表现为糖尿病，提示Foxm1b在正常的β细胞功能中起作用。对突变胰腺的检查显示，在4至9周龄之间，β细胞团逐渐消失。我们假设Foxm1b对于维持正常的β细胞质量和调节β细胞的周转是必不可少的。我们预测Foxm1b对于胰腺和β细胞的再生以及β细胞的代偿都是至关重要的。为了验证这些假设，我们将在整个胰腺中灭活Foxm1b，或者仅在胰腺内分泌细胞中灭活Foxm1b。彻底了解Foxm1b对β细胞质量的调节可能会导致在糖尿病患者中维持β细胞质量和促进β细胞增殖的策略。

Beta cell mass is dynamic, changing throughout the life of the organism in response to metabolic alterations and demands. Increases in beta cell mass are thought to occur via both replication of existing beta cells and beta cell neogenesis from stem cell progenitors. Diabetes results from an absolute (Type 1) or relative (Type 2) inadequate functional beta cell mass. Thus, genes and pathways involved in maintaining or altering beta cell mass are candidates for being affected in diabetic individuals. Functional analysis of these genes may lead to new therapeutic strategies for increasing existing beta cell mass in diabetic patients and/or facilitate the production of beta cells in vitro from embryonic or stem cells. The Foxm1b transcription factor is highly expressed in proliferating cells and activates cell cycle genes. Liver-specific Foxm1b inactivation impairs liver regeneration following partial hepatectomy. These results prompted us to examine whether Foxm1b functions similarly in pancreas and/or beta cell regeneration and compensation. We found that Foxm1b is highly expressed in embryonic and neonatal endocrine cells, when many of cells are proliferating. Using a Cre-lox strategy, we made mice with a pancreas-specific Foxm1b deletion to examine its role in pancreas regeneration following partial pancreatectomy. Mice lacking Foxm1b in their entire pancreas were glucose intolerant at 6 weeks of age and overtly diabetic by 9 weeks of age, suggesting a role for Foxm1b in normal beta cell function. Examination of mutant pancreata revealed a gradual loss of beta cell mass between 4 and 9 weeks of age. We hypothesize that Foxm1b is essential to maintain normal beta cell mass and regulate betaa cell turnover. We predict that Foxm1b is critical for pancreas and beta cell regeneration and for beta cell compensation. To test these hypotheses we will inactivate Foxm1b in the entire pancreas, or exclusively in pancreatic endocrine cells. A thorough understanding of Foxm1b regulation of beta cell mass may lead to strategies for maintaining beta cell mass and enhancing beta cell proliferation in diabetics.