Foxm1b in endocrine pancreas growth and regeneration

β细胞群是动态的，在生物体的整个生命过程中响应于代谢改变和需求而变化。β细胞质量的增加被认为是通过现有β细胞的复制和来自干细胞祖细胞的β细胞新生而发生的。糖尿病由绝对（1型）或相对（2型）功能性β细胞质量不足引起。因此，基因 并且参与维持或改变β细胞群的途径是糖尿病个体中受影响的候选者。这些基因的功能分析可能会导致新的治疗策略，增加现有的β细胞质量在糖尿病患者和/或促进生产β细胞在体外从胚胎或干细胞。Foxm 1b转录因子在增殖细胞中高度表达并激活细胞周期基因。肝脏特异性Foxm 1b失活损害部分肝切除术后的肝再生这些结果促使我们研究Foxm 1b在胰腺和/或β细胞再生和补偿中是否具有相似的功能。我们发现Foxm 1b在胚胎和新生儿的内分泌细胞中高表达，当许多细胞增殖时。使用Cre-lox策略，我们制作了胰腺特异性Foxm 1b缺失的小鼠，以检查其在胰腺再生中的作用， 胰腺部分切除术在整个胰腺中缺乏Foxm 1b的小鼠在6岁时葡萄糖不耐受 9周龄时明显患有糖尿病，表明Foxm 1b在正常β细胞功能中的作用。对突变胰腺的检查显示，在4至9周龄之间，β细胞质量逐渐丧失。我们假设Foxm 1b对维持正常的β细胞群和调节β细胞更新是必不可少的。我们预测Foxm 1b对胰腺和β细胞再生以及β细胞补偿至关重要。为了验证这些假设，我们将在整个胰腺或胰腺内分泌细胞中检测Foxm 1b。彻底了解Foxm 1b对β细胞质量的调节可能会导致维持β细胞质量和增强糖尿病患者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.