Role of Carotid Bodies in Glucose Homeostasis in Humans

颈动脉体在人类血糖稳态中的作用

基本信息

批准号：
8055861
负责人：
Erica Ariece Wehrwein
金额：
$ 5.13万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8055861
关键词：
Acute Address Area Bilateral Blood Glucose Canis familiaris Carotid Body Catecholamines Cells Chemoreceptors Chronic Obstructive Airway Disease Clinic Conscious Denervation Diabetes Mellitus Disease Environment Environmental air flow Euglycemic Clamping Excision Failure Functional disorder Glomus Cell Glomus Tumor Glucagon Glucose Glucose Clamp Goals Health Human Hydrocortisone Hyperglycemia Hyperinsulinism Hyperoxia Hypoglycemia Hypoxia Infusion procedures Insulin Mediating Metabolic syndrome Metabolism Operative Surgical Procedures Oxygen Oxygen measurement, partial pressure, arterial Patients Physiological Play Public Health Regulation Research Research Personnel Role Site Sleep Apnea Syndromes Somatotropin Testing Whole-Body Counter blood glucose regulation counterregulation experience glucose disposal glucose production glucose uptake human subject improved insulin sensitivity interest metabolic abnormality assessment novel patient population prevent public health relevance receptor respiratory response sensor

项目摘要

DESCRIPTION (provided by applicant): Whole body glucose homeostasis is of critical importance and failure to properly regulate blood glucose is associated with or causes a myriad of health problems. There is controversy as to which of the many proposed glucose-sensing sites are most important in responding to acute changes in blood glucose. Recently the carotid bodies have emerged as a potentially important site in blood glucose regulation. However, the role of the carotid bodies in regulating whole body glucose homeostasis in humans has undergone minimal exploration. Therefore we aim to test the overall hypothesis that carotid bodies play an integral role in blood glucose sensing and regulation. By using euglycemic and hypoglycemic glucose clamps in conscious human subjects with intact and denervated carotid bodies, we will examine the effect of altered oxygen saturation (both hypoxic and hyperoxic) on whole body glucose homeostasis. Specifically, we will: 1) perform hyperinsulinemic hypoglycemic glucose clamps during normoxia and hyperoxia; a maneuver that should suppress the ability of type 1 glomus cells in the carotid bodies to sense hypoglycemia and therefore will limit the counterregulatory response to hypoglycemia, 2) perform hyperinsulinemic euglycemic glucose clamps during normoxia and hypoxia a maneuver that should stimulate the type 1 glomus cells in the carotid bodies and reduce glucose disappearance and insulin suppression of glucose production in spite of euglycemia and hyperinsulinemia, and 3) compare the physiological responses to hyperinsulinemic hypoglycemic glucose clamps in patients who have undergone bilateral carotid body denervation for the treatment of glomus tumor.

描述（由申请人提供）：全身葡萄糖稳态至关重要，未能正确调节血糖会导致多种健康问题。对于许多提议的葡萄糖传感位点中哪一个对于响应血糖的急性变化最重要，存在争议。最近，颈动脉体已成为血糖调节的潜在重要部位。然而，人们对颈动脉体在调节人体全身葡萄糖稳态中的作用的探索还很少。因此，我们的目的是检验颈动脉体在血糖传感和调节中发挥不可或缺的作用的总体假设。通过在具有完整和去神经颈动脉体的清醒人类受试者中使用正常血糖和低血糖葡萄糖钳，我们将检查改变的氧饱和度（缺氧和高氧）对全身葡萄糖稳态的影响。具体来说，我们将：1）在常氧和高氧期间进行高胰岛素低血糖葡萄糖钳夹；该操作应抑制颈动脉体中 1 型血管球细胞感知低血糖的能力，从而限制对低血糖的反调节反应，2) 在常氧和缺氧期间进行高胰岛素正常血糖钳夹操作应刺激 1 型血管球细胞尽管存在血糖正常和高胰岛素血症，但仍能减少颈动脉体内的葡萄糖消失和胰岛素对葡萄糖产生的抑制，以及 3) 比较接受双侧颈动脉体去神经术治疗血管球瘤的患者对高胰岛素低血糖葡萄糖钳夹的生理反应。