Keystone Symposia on Cellular and Molecular Basis of Metabolic Disorders Series

摘要 该提案要求支持为期5年的Keystone研讨会系列会议，讨论代谢紊乱的细胞和分子基础。2010年及以后的会议将建立在Keystone Symposia在这一领域的最佳传统基础上，包括前沿研究，动态批判性讨论，跨学科发现和解决问题，建立网络和合作，以及培养下一代研究人员。第一年包括六次会议。脂肪组织生物学会议考虑了血管生成在脂肪组织扩张中的作用;白色脂肪-棕色脂肪的争论;昼夜节律钟对协调食物摄入和代谢平衡活动的激素和神经信号的贡献;以及中枢和外周信号在由抗精神病药和抗逆转录病毒药物等治疗方案引起的意外脂肪营养不良性疾病中的作用。同时举行的食欲，代谢和体重神经元控制会议解决了深入了解体重稳态和功能障碍导致肥胖和相关疾病的复杂机制的关键需求。这些联席会议利用中枢神经系统和脂肪组织之间的关键相互作用来控制能量稳态，并探索与肥胖和糖尿病发病相关的这种沟通功能障碍。核 受体：信号传导，基因调控和癌症旨在了解核受体（NR）的配体依赖性分子作用-包括亚细胞定位，跨基因组结合以及与蛋白质组的相互作用-如何与它们在生理和病理生理过程中的作用联系起来，包括细胞调节的癌症。这次会议还审查了作为药物开发目标的NR。并发核受体：发展，生理学和疾病会议重点关注NR在发育，生理学和代谢中的作用，以及它们在人类疾病中的作用。这强调 转录控制的分子机制、正常发育和生理学、疾病起始和进展、治疗干预的方法和由NR功能障碍引起的疾病的整合。胰岛生物学批判性地讨论了胰岛研究的几个领域的进展，包括发育，再生，干细胞，转录因子，新的信号通路，细胞生物学，遗传学，基因调控，药物靶向和新兴技术。本次会议明确提出了设计有效方法以改善2型糖尿病患者胰腺ss细胞功能和存活率以及产生用于1型糖尿病移植的ss细胞的最终目标。同期的糖尿病会议通过在许多不同领域的研究，探讨2型糖尿病的发病机制和可能的治疗方法，并利用遗传，基因组和生理学的观点。目的是解决2型糖尿病及其相关代谢紊乱发展的复杂生物学基础。会议还讨论了旨在深入研究2型糖尿病分子发病机制的新技术进展。

ABSTRACT This proposal requests support for a 5-year Keystone Symposia meeting series on the Cellular and Molecular Basis of Metabolic Disorders. The meetings for 2010 and beyond will build upon the best of Keystone Symposia's tradition in this area including cutting-edge research, dynamic critical discussions, interdisciplinary discovery and problem-solving, building networks and collaborations, and developing the next generation of investigators. Year 1 consists of six meetings. The Adipose Tissue Biology meeting considers the role of angiogenesis in adipose tissue expansion; the white fat-brown fat debate; the contribution of the circadian clock to hormonal and neural signals coordinating food intake and activity for metabolic balance; and the role of central and peripheral signals in the unanticipated lipodystrophic disorders resulting from such therapeutic regimens as antipsychotics and anti-retrovirals. The concurrent Neuronal Control of Appetite, Metabolism and Weight meeting addresses the crucial need for deeper understanding of the complex mechanisms of body weight homeostasis and dysfunctions leading to obesity and associated disorders. These joint meetings take advantage of critical interaction between the CNS and adipose tissue for control of energy homeostasis, and exploring dysfunction in this communication associated with the onset of obesity and diabetes. Nuclear Receptors: Signaling, Gene Regulation, and Cancer aims to understand how the ligand-dependent molecular actions of Nuclear Receptors (NRs) - including subcellular localization, binding across the genome, and interaction with the proteome - connect to their roles in physiological and pathophysiological processes, including hormone-regulated cancers. This meeting also examines NRs as targets for drug development. The concurrent Nuclear Receptors: Development, Physiology and Disease meeting focuses on the roles of NRs in development, physiology, and metabolism, and on their involvement in human disease. This emphasizes integration of molecular mechanisms of transcriptional control, normal development and physiology, disease initiation and progression, approaches to therapeutic intervention, and diseases that arise from NR dysfunction. Islet Biology critically discusses advances in several areas of islet research including development, regeneration, stem cells, transcription factors, novel signaling pathways, cell biology, genetics, gene regulation, drug targeting, and emerging technologies. This meeting explicitly addresses the ultimate goal of designing effective approaches to improve pancreatic ss-cell function and survival in Type 2 diabetes and generating ss-cells for transplantation in Type 1 diabetes. The concurrent Diabetes meeting explores Type 2 diabetes pathogenesis and possible therapeutics via research in many different fields, and capitalizes on genetic, genomic and physiological perspectives. The aim is to resolve the complex biology underpinning development of Type 2 diabetes and its associated metabolic disorders. The meeting also discusses new technical advances designed to penetrate the molecular pathogenesis of Type 2 diabetes.