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Cell Cycle Regulators in Diabetes and Obesity

糖尿病和肥胖症中的细胞周期调节剂

基本信息

批准号：
7967579
负责人：
Sushil Rane
金额：
$ 52.01万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7967579
关键词：
Address Adipose tissue Alleles Animal Model Beta Cell Brown Fat CDKN2A gene Cell Cycle Cell Cycle Progression Cells Chronic Disease Cyclin-Dependent Kinase 4 Data Defect Diabetes Mellitus Diabetic mouse Diet Disease E2F transcription factors E2F1 gene Epidemiology Equilibrium Event Exhibits Family Fatty acid glycerol esters Future Generations Gene Targeting Gonadal Steroid Hormones Growth Homeostasis Hyperplasia Infertility Inherited Insulin Investigation Life Expectancy Life Style Malignant Neoplasms Mediating Metabolic Metabolic Diseases Modeling Molecular Mus Muscle Muscle Development Mutation Obesity Obesity associated disease Organ PPAR gamma Pancreas Pathway interactions Phosphorylation Play Prevalence Process Production Public Health Regulation Retinoblastoma Retinoblastoma Protein Role Societies Staging Structure of beta Cell of islet Thermogenesis Tissues adipocyte differentiation blood glucose regulation cancer risk design embryonic stem cell energy balance feeding glucose tolerance lipid biosynthesis mouse model non-diabetic obesity treatment precursor cell sedentary transcription factor

项目摘要

In this proposal we will use mouse models that have mutations in the Cdk4 locus. Cdk4-/- mice are diabetic and lean, and in contrast, Cdk4R24C mice are non-diabetic and heavier. These observations are consistent with the documented, albeit not very well characterized, role of the RB/E2F pathway in adipogenesis amd muscle differentiation. Since Cdk4 is an upstream regulator of the E2F-RB pathway, we hypothesize that Cdk4 activity may regulate adipogenesis and muscle development and function. Further, the effect of Cdk4 on production of insulin, sex hormones and glucose regulation may impact the energy balance in the Cdk4R24C model. We are studying mechanisms of glucose tolerance and energy homeostasis by evaluating CDk4-dependent functions in different metabolic organs in the Cdk4 mice. The findings are revealing important role of Cdk4 in process that modulate energy balance.

在本提案中，我们将使用在Cdk4基因座中具有突变的小鼠模型。Cdk4-/-小鼠是糖尿病和瘦的，相比之下，Cdk4R24C小鼠是非糖尿病和更重的。这些观察结果与记录的RB/E2F途径在脂肪形成和肌肉分化中的作用一致，尽管没有很好地表征。由于Cdk4是E2F-RB通路的上游调节因子，我们推测Cdk4活性可能调节脂肪形成和肌肉发育和功能。此外，Cdk4对胰岛素、性激素和葡萄糖调节的产生的作用可能影响Cdk4R24C模型中的能量平衡。我们正在研究葡萄糖耐量和能量平衡的机制，通过评估CDK4依赖的功能，在不同的代谢器官中的Cdk4小鼠。这些发现揭示了Cdk 4在调节能量平衡过程中的重要作用。