Peripheral clocks in metabolism and diabetes

新陈代谢和糖尿病的外周时钟

基本信息

批准号：
7393676
负责人：
Radu Daniel RUDIC
金额：
$ 9.11万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7393676
关键词：
Accounting Adipose tissue Aorta Behavior Behavioral Blood Blood Glucose Blood Pressure Cardiovascular Diseases Characteristics Circadian Rhythms Constitution Daily Defect Development Diabetes Mellitus Diabetic mouse Diet Environmental Risk Factor Evolution Exhibits Fatty acid glycerol esters Feedback Functional disorder Gene Deletion Gene Expression Genes Genetic Glucose Homeostasis Hormones Hypoglycemia Hypoglycemic Agents Impairment Insulin Leptin Light Lipids Measures Mediating Metabolic Control Metabolism Modeling Molecular Molecular Profiling Mus Mutation Neuraxis Non-Insulin-Dependent Diabetes Mellitus Organ Pattern Peptides Periodicity Peripheral Phenotype Physiological Physiology Plasminogen Activator Inhibitor 1 Proteins Regulation Relative (related person)Role Signal Transduction Staging Time Tissues Triglycerides Variant Wild Type Mouse adipokines adiponectin blood glucose regulation circadian pacemaker diabetic enzyme activity feeding gene function glucose tolerance insulin sensitivity lipid metabolism resistin response

项目摘要

DESCRIPTION (provided by applicant): The proposal examines the relationship between circadian rhythms, metabolism, and diabetes. Circadian rhythms are daily variations in physiology and function. Metabolism, including glucose and lipid homeostasis, is known to exhibit circadian variation. However, the mechanisms governing these rhythms are not known. Analysis of gene expression of aortic tissue revealed that the adipokines leptin, adiponectin, and resistin followed circadian rhythmicity. Regulatory control of these secreted peptides and proteins which are important in glucose and lipid homeostasis is still not fully understood. In specific aim 1, adipokine release will be assessed in mice with a defective circadian clock. In Specific Aim 2, the impact of molecular clock dysfunction on lipid homeostasis will be assessed by measuring lipid profiles, triglyceride clearance, secretion, and lipid metabolizing activity. Moreover, though the molecular clock is known to be perturbed in models of diabetes, if and how the molecular clock impacts the evolution of diabetes is unknown. In Specific Aim 3, the influence of a disrupted molecular clock will be examined in diabetes by implementing mouse models of diabetes. In summary, though light may be the dominant signal to set circadian rhythms in the central nervous system, other environmental factors may preside in the periphery. While environmental influences may dominate in the constitution of diabetes, they may interact with oscillating gene function under control of the metabolic clock in a way that amplifies or diminishes their influence.

描述（由申请人提供）：该提案研究了昼夜节律，代谢和糖尿病之间的关系。昼夜节律是生理和功能的每日变化。已知新陈代谢，包括葡萄糖和脂质稳态，表现出昼夜节律的变化。但是，尚不清楚控制这些节奏的机制。主动脉组织基因表达的分析表明，脂肪因子瘦素，脂联素和抵抗素跟随昼夜节律。这些在葡萄糖和脂质稳态中很重要的分泌肽和蛋白质的调节控制仍未完全了解。在特定的目标1中，将在昼夜节律有缺陷的小鼠中评估脂肪因子释放。在特定的目标2中，将通过测量脂质谱，甘油三酸酯清除率，分泌和脂质代谢活性来评估分子时钟功能障碍对脂质稳态的影响。此外，尽管已知分子时钟在糖尿病模型中受到干扰，但分子时钟如何影响糖尿病的演变。在特定的目标3中，将通过实现糖尿病小鼠模型来检查被干扰的分子钟的影响。总而言之，尽管光线可能是在中枢神经系统中设置昼夜节律的主要信号，但其他环境因素可能会主持外围。尽管环境影响可能在糖尿病的构成中占主导地位，但它们可能会以放大或减少其影响的方式控制代谢时钟的振荡基因功能。