Cell Cycle Regulators in Diabetes and Obesity

在本提案中，我们将使用在细胞周期基因位点中具有突变的小鼠模型。我们正在研究葡萄糖耐量和能量平衡的机制，通过评估在小鼠不同的代谢器官的功能，在几个细胞周期基因的突变。这些发现揭示了Cdks和TGF-β蛋白在调节能量平衡过程中的重要作用。我们正在使用组织特异性条件小鼠和转基因小鼠，使用Cre-loxP技术来消除或激活候选细胞周期蛋白的表达。这些小鼠模型的特征在于评估其葡萄糖耐量和能量消耗表型。在适当的情况下，我们通过研究不同的葡萄糖/胰岛素反应组织/细胞，用高脂饮食、运动和/或寒冷暴露来挑战小鼠，以进一步了解细胞周期蛋白在能量代谢中的作用。

In this proposal we will use mouse models that have mutations in the Cell cycle gene loci. We are studying mechanisms of glucose tolerance and energy homeostasis by evaluating functions in different metabolic organs in mice harboring mutations in several cell cycle genes. The findings are revealing important role of Cdks and TGF-beta proteins in processes that modulate energy balance. We are employing tissue-specific conditional mice and transgenic mice to abalte or activate the expression of candidate cell cycle proteins using Cre-loxP technology. These mouse models are them charaterized to evalaute their glucose tolerance and energy expenditure phenotypes. Where appropriate we are challenging the mice with high-fat diet, exercise and/or cold exposure to further understand the role of cell cycle protein in energy metabolism via study of distinct glucose/insulin responsive tissues/cells.