Foxm 1b endocrine pancreas growth and regeneration

3细胞团是动态的，在生物体的整个生命过程中响应于代谢改变而变化， 要求。认为3细胞质量的增加通过现有3细胞和3细胞的复制发生。 从干细胞祖细胞再生。糖尿病是绝对的（1型）或相对的（2型） 功能性3细胞团不足。因此，参与维持或改变3细胞质量的基因和途径 在糖尿病患者中是受影响的候选者。对这些基因的功能分析可能会导致新的 用于增加糖尿病患者中现有的β细胞质量和/或促进β细胞生成的治疗策略 3来自胚胎或干细胞的体外细胞。Foxml转录因子在哺乳动物中高度表达。 增殖细胞并激活细胞周期基因。肝脏特异性Foxml失活损害肝再生 部分肝切除术后这些结果促使我们研究Foxml在 胰腺和/或3细胞再生和补偿。我们发现Foxml在人乳腺癌组织中高表达， 胚胎和新生儿内分泌细胞，此时许多细胞正在增殖。使用Cre-lox策略，我们 制造了胰腺特异性Foxml缺失的小鼠，以检查其在胰腺再生中的作用， 胰腺部分切除术在其整个胰腺中缺乏Foxm 1的小鼠在6周时是葡萄糖不耐受的。 这表明Foxml在正常3细胞中具有意想不到的作用， 功能对突变胰腺的检查显示，在4周和9周之间， 年龄我们假设Foxml对于维持正常的3细胞团和调节3细胞更新是必不可少的。 我们预测Foxml对于胰腺和3细胞再生以及3细胞补偿是关键的。测试 这些假设，我们将在整个胰腺，或专门在胰腺内分泌 细胞我们将在不同的B细胞群扩增模型中测试Foxml的需求，包括 妊娠和高脂肪饮食/胰岛素抵抗。深入了解Foxml对3细胞团的调控 可能导致维持糖尿病患者的3细胞群和增强3细胞增殖的策略。

3 cell mass is dynamic, changing throughout the life of the organism in response to metabolic alterations and demands. Increases in 3 cell mass are thought to occur via both replication of existing 3 cells and 3 cell neogenesis from stem cell progenitors. Diabetes results from an absolute (Type 1) or relative (Type 2) inadequate functional 3 cell mass. Thus, genes and pathways involved in maintaining or altering 3 cell mass are candidates for being affected in diabetic individuals. Functional analysis of these genes may lead to new therapeutic strategies for increasing existing 3 cell mass in diabetic patients and/or facilitate the production of 3 cells in vitro from embryonic or stem cells. The Foxml transcription factor is highly expressed in proliferating cells and activates cell cycle genes. Liver-specific Foxml inactivation impairs liver regeneration following partial hepatectomy. These results prompted us to examine whether Foxml functions similarly in pancreas and/or 3 cell regeneration and compensation. We found that Foxml 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 Foxml deletion to examine its role in pancreas regeneration following partial pancreatectomy. Mice lacking Foxml in their entire pancreas were glucose intolerant at 6 weeks of age and overtly diabetic by 9 weeks of age, suggesting an unexpected role for Foxml in normal 3 cell function. Examination of mutant pancreata revealed a gradual loss of 3 cell mass between 4 and 9 weeks of age. We hypothesize that Foxml is essential to maintain normal 3 cell mass and regulate 3 cell turnover. We predict that Foxml is critical for pancreas and 3 cell regeneration and for 3 cell compensation. To test these hypotheses we will inactivate Foxml in the entire pancreas, or exclusively in pancreatic endocrine cells. We will test the requirement for Foxml in different models of b cell mass expansion including pregnancy and high fat diet/insulin resistance. A thorough understanding of Foxml regulation of 3 cell mass may lead to strategies for maintaining 3 cell mass and enhancing 3 cell proliferation in diabetics.