Foxm 1b endocrine pancreas growth and regeneration

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的变化而变化 要求。3个细胞质量的增加被认为是通过复制现有的3个细胞和3个细胞而发生的 干细胞前体细胞的新生。糖尿病由绝对型(1型)或相对型(2型)引起 功能不全的3个细胞团。因此，与维持或改变细胞团有关的基因和途径 是糖尿病患者可能受到影响的对象。对这些基因的功能分析可能会导致新的 增加糖尿病患者现有的3细胞质量和/或促进产生 3体外培养胚胎细胞或干细胞。FoxML转录因子在细胞中高度表达 促进细胞增殖，激活细胞周期基因。肝脏特异性Foxml失活损害肝脏再生 在部分肝切除后。这些结果促使我们检查Foxml是否在 胰腺和/或3个细胞的再生和代偿。我们发现Foxm1在 胚胎和新生儿的内分泌细胞，此时许多细胞正在增殖。使用CRE-LOX策略，我们 建立胰腺特异性Foxm1缺失的小鼠模型，研究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foxml的小鼠在6周后出现糖耐量异常 年龄和9周龄时明显糖尿病，这表明Foxml在正常3细胞中发挥了意想不到的作用 功能。对突变胰腺的检查显示，在4至9周内，3个细胞团逐渐消失 年龄。我们推测，FOXML对于维持正常的3细胞质量和调节3细胞的周转是必不可少的。 我们预测Foxm1对胰腺和3细胞的再生以及3细胞的代偿都是至关重要的。为了测试 这些假设我们将使整个胰腺中的FoxML失活，或仅在胰腺内分泌中失活 细胞。我们将在不同的b细胞扩增模型中测试对foxml的需求，包括 怀孕和高脂肪饮食/胰岛素抵抗。深入了解FOXML对3个细胞团的调控 可能导致糖尿病患者维持3细胞质量和促进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.