Peripheral clocks in metabolism and diabetes

新陈代谢和糖尿病的外周时钟

• 批准号: 6902767
• 负责人: Radu Daniel RUDIC
• 金额: $ 2.96万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6902767
• 关键词: adipose tissue; circadian rhythms; diabetes mellitus genetics; dietary lipid; disease /disorder model; gene environment interaction; gene expression profiling; glucose metabolism; hormone regulation /control mechanism; laboratory mouse; leptin; lipid metabolism; metabolism; noninsulin dependent diabetes mellitus; nutrition related tag; pathologic process; peptide hormone; photobiology; adipose tissue; circadian rhythms; diabetes mellitus genetics; dietary lipid; disease /disorder model; gene environment interaction; gene expression profiling; glucose metabolism; hormone regulation /control mechanism; laboratory mouse; leptin; lipid metabolism; metabolism; noninsulin dependent diabetes mellitus; nutrition related tag; pathologic process; peptide hormone; photobiology

DESCRIPTION (provided by applicant): The immediate goals of Radu Daniel Rudic, Ph.D. are to expand his experience and knowledge to the area of diabetes research. Ultimately his plan is to develop a niche that will facilitate his transition as an independent investigator in academia. The proposed research will be performed at the University of Pennsylvania. 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）： Radu Daniel Rudic博士的直接目标将他的经验和知识扩展到糖尿病研究领域。最终，他的计划是开发一个利基市场，以促进他在学术界的独立调查员的过渡。拟议的研究将在宾夕法尼亚大学进行。 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。