Role of Carotid Bodies in Glucose Homeostasis in Humans

颈动脉体在人类血糖稳态中的作用

• 批准号: 7897391
• 负责人: Erica Ariece Wehrwein
• 金额: $ 4.76万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 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/7897391
• 关键词: Acute; Bilateral; Blood Glucose; Carotid Body; Chemoreceptors; Chronic Obstructive Airway Disease; Conscious; Denervation; Diabetes Mellitus; Environmental air flow; Euglycemic Clamping; Failure; Functional disorder; Glomus Cell; Glomus Tumor; Glucose; Glucose Clamp; Health; Human; Hyperinsulinism; Hyperoxia; Hypoglycemia; Hypoxia; Insulin; Metabolic syndrome; Metabolism; Oxygen; Patients; Physiological; Play; Public Health; Regulation; Role; Site; Sleep Apnea Syndromes; Testing; blood glucose regulation; glucose production; human subject; interest; public health relevance; receptor; response; sensor

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. PUBLIC HEALTH RELEVANCE: In the interest of public health concerns such as diabetes, sleep apnea, chronic obstructive pulmonary disease, and the metabolic syndrome, this study will investigate the possibility of a common mechanism for patients that have dysfunction in both glucose handling and ventilation. By examining the role of the carotid body chemoreceptors as multi-modal receptors that simultaneously sense blood glucose levels and oxygen, we will determine whether the carotid bodies play a role as an integrated sensor that influences both metabolism and ventilation in healthy humans.

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。 公共健康相关性：为了解决糖尿病、睡眠呼吸暂停、慢性阻塞性肺疾病和代谢综合征等公共健康问题，本研究将探讨针对葡萄糖处理和通气功能障碍的患者建立共同机制的可能性。通过检查颈动脉体化学感受器作为同时感知血糖水平和氧气的多模式受体的作用，我们将确定颈动脉体是否发挥作为影响健康人体新陈代谢和通气的综合传感器的作用。