Neurobiological Correlates of Autonomic Dysfunction and Insulin Resistance

描述(申请人提供)：2型糖尿病(T2D)在美国是一个重要的公共健康负担，影响着20岁以上的2000多万人。糖尿病对许多器官系统都有致病作用，导致与肾功能、视力和心血管系统相关的并发症。T2D的一个先兆是胰岛素抵抗。对胰岛素特别敏感的一个器官是大脑，在那里胰岛素被积极地通过血脑屏障运输。然而，到目前为止，很少有研究调查胰岛素抵抗患者的大脑结构和功能是如何改变的。大脑控制着身体中的许多生理系统，其中一个系统是自主神经系统。患有胰岛素抵抗和T2D的人的自主神经系统活动发生变化，这可能会增加他们死于心血管疾病的风险。本研究的目的是研究特定大脑区域腹侧纹状体的活动如何与空腹胰岛素水平和自主神经功能相关。这项研究非常符合国家糖尿病、消化和肾脏疾病研究所的战略目标，特别是在肥胖综合生物学计划范围内，该计划支持“基础和临床研究，调查导致肥胖的神经和内分泌机制以及肥胖，特别是2型糖尿病的病理生理后果。”这项申请将使申请者能够接受作为T2D基础的内分泌系统的生理学和病理学方面的正式培训，并将他的功能神经成像培训扩展到包括先进技术，以了解大脑区域之间的相互作用以及它们如何随着生理条件的变化而变化。结合自主神经活性的测量，这项研究将进一步加深我们对胰岛素抵抗改变自主神经活性并增加致病风险的机制的理解。 与公共卫生相关：胰岛素抵抗是2型糖尿病的先兆，2型糖尿病是美国一种公共卫生流行病，困扰着2000多万人。2型糖尿病可能通过自主神经系统的改变增加心血管疾病的风险。这项拟议的研究将研究静息大脑活动如何与胰岛素抵抗和自主神经活动相关，以帮助理解胰岛素和自主神经功能之间的关系。

DESCRIPTION (provided by applicant): Type 2 Diabetes (T2D) is a significant public health burden in the United States, affecting more than 20 million people over the age of 20. Diabetes has pathogenic effects on numerous organ systems, causing complications related to kidney function, vision, and the cardiovascular system. One precursor to T2D is insulin resistance. One organ that is particularly sensitive to insulin is the brain, where insulin is actively transported across the blood brain barrier. To date, however, few human studies have investigated how brain structure and function are altered in individuals with insulin resistance. The brain controls numerous physiological systems in the body, and one such system is the autonomic nervous system. Individuals with insulin resistance and T2D have alterations in their autonomic nervous system activity that can increase their risk for death due to cardiovascular disease. The goal of the present proposal is to investigate how activity in one particular brain region, the ventral striatum, covaries with fasting insulin levels and autonomic function. This research fits well within the strategic aims of the National Institute of Diabetes and Digestive and Kidney Diseases, especially within the Integrative Biology of Obesity Program, which supports "basic and clinical research investigating the neural and endocrine mechanisms contributing to obesity and the pathophysiological consequences of obesity, particularly type 2 diabetes." This application will enable the Applicant to receive formal training in the physiology and pathology of the endocrine system that underlies T2D, as well as extend his training in functional neuroimaging to include advanced techniques to understand the interactions between brain regions and how they covary with physiological conditions. Combined with the measurement of autonomic activity, this research will further our understanding of the mechanisms by which insulin resistance alters autonomic activity and increases risk for pathogenic outcomes. PUBLIC HEALTH RELEVANCE: Insulin resistance is a precursor to Type 2 Diabetes, a public health epidemic in the United States afflicting more than 20 million people. Type 2 Diabetes increases risk for cardiovascular disease, possibly through alterations in the autonomic nervous system. The proposed study will examine how resting brain activity covaries with insulin resistance and autonomic activity to help understand the pathways by which insulin and autonomic function are related.