Neurobiological Correlates of Autonomic Dysfunction and Insulin Resistance

描述（由申请人提供）：2型糖尿病（T2D）是美国的一个重大公共卫生负担，影响20岁以上的2000多万人。糖尿病对许多器官系统具有致病作用，引起与肾功能、视力和心血管系统相关的并发症。T2D的一个前兆是胰岛素抵抗。对胰岛素特别敏感的一个器官是大脑，胰岛素在大脑中被积极地运输穿过血脑屏障。然而，迄今为止，很少有人类研究调查了胰岛素抵抗个体的大脑结构和功能如何改变。大脑控制着身体中的许多生理系统，其中一个系统就是自主神经系统。胰岛素抵抗和T2D患者的自主神经系统活动发生改变，这可能会增加他们因心血管疾病而死亡的风险。本研究的目的是研究腹侧纹状体这一特定脑区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中，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的病理生理后果，特别是2型糖尿病。“这项申请将使申请人能够接受T2D基础内分泌系统生理学和病理学的正式培训，并扩展他在功能性神经成像方面的培训，以包括先进的技术来了解大脑区域之间的相互作用以及它们如何与生理条件协变。结合自主活动的测量，这项研究将进一步加深我们对胰岛素抵抗改变自主活动和增加致病风险的机制的理解。 公共卫生相关性：胰岛素抵抗是2型糖尿病的前兆，2型糖尿病是美国的一种公共卫生流行病，困扰着2000多万人。2型糖尿病增加心血管疾病的风险，可能是通过改变自主神经系统。这项拟议中的研究将研究静息脑活动如何与胰岛素抵抗和自主活动协变，以帮助了解胰岛素和自主功能相关的途径。

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.