Mechanism of Glucose-dependent insulinotropic polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome

葡萄糖依赖性促胰岛素多肽（GIP）对姿势性心动过速综合征内脏静脉电容的影响机制

• 批准号: 10669789
• 负责人: Cyndya Adriana Shibao
• 金额: $ 84.79万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669789
• 关键词: Adult; Affect; Age; Blood; Blood Pressure; Blood Volume; Blood flow; Body mass index; C-Peptide; Canis familiaris; Carbohydrates; Cardiac Output; Chronic; Clinical; Communities; Consumption; Continuous Positive Airway Pressure; Cross-Over Studies; Data; Diet; Disease; Dose; Double-Blind Method; Eating; Electric Capacitance; Endothelial Cells; Enrollment; Experimental Designs; Fasting; Functional disorder; Glucose; Goals; Head; Heart Rate; Hormones; Human; Human body; Ingestion; Intake; Intestines; Intravenous infusion procedures; Knowledge; Measures; Mesentery; Oral; Orthostatic tachycardia; Patients; Peripheral Resistance; Persons; Physiological; Polypeptide Hormones; Positioning Attribute; Postprandial Period; Postural Orthostatic Tachycardia Syndrome; Posture; Property; Quality of life; Randomized; Research; Saline; Smooth Muscle Myocytes; Splanchnic Circulation; Stroke Volume; Superior mesenteric artery structure; Supination; Surveys; Symptoms; Tachycardia; Techniques; Testing; Time; United States; Veins; Venous; antagonist; arteriole; electric impedance; falls; gastric inhibitory polypeptide receptor; hemodynamics; improved; incretin hormone; innovation; insulin secretion; novel; positive airway pressure; receptor; response; symptom treatment; young woman

Project summary Postural Tachycardia Syndrome (POTS) affects ~3 million adults in the United States. These patients have a poor quality of life due to chronic presyncopal symptoms and tachycardia that occur upon standing. Our research has shown that meals rich in carbohydrates significantly exacerbate presyncopal symptoms in POTS, however, the underlying mechanism that explains this clinical observation remains unknown. Accordingly, our group conducted a preliminary study to evaluate the pathophysiology of POTS’ excessive orthostatic tachycardia after glucose intake; we surveyed the hemodynamic and neurohormonal changes that occurred after a 75-gr oral glucose challenge for up to 2-hrs (postprandial period) in POTS patients and healthy controls. Compared with fasting conditions, the ingestion of glucose worsened upright tachycardia in POTS patients, which was associated with a more robust reduction in upright stroke volume compared with healthy controls. With regards to the disproportionate decrease in upright stroke volume in POTS patients, this could, in part, be explained by a significant blood pooling in the splanchnic circulation. The splanchnic circulation is the largest blood volume reservoir of the human body, storing ~25% of the total blood volume. Upon standing, there is a significant blood pooling, which occurs mostly in the splanchnic veins. Finally, our study has also shown that 30-min after the ingestion of 75-gr of glucose, POTS patients had a selectively increased secretion of the glucose-dependent insulinotropic polypeptide (GIP) hormone compared with healthy controls. This hormone has vasodilatory properties in the splanchnic circulation. Importantly, the increase in GIP secretion was time-dependently associated with a fall in upright stroke volume after glucose intake in POTS. Consequently, these findings point to the potential contribution of GIP in the pathophysiology of the increased postprandial orthostatic tachycardia and presyncopal symptoms in POTS patients. As such, the overall goal of this proposal is to investigate the mechanisms underlying the exacerbation of orthostatic tachycardia and POTS presyncopal symptoms in response to glucose ingestion. Specifically, we will evaluate the contribution of GIP on the changes in the splanchnic venous capacitance after oral glucose and during upright posture in POTS patients.

项目摘要 姿势心动过速综合征（POTS）在美国影响约300万成年人。这些患者有 站立后发生的慢性前症状和心动过速导致的生活质量差。我们的 研究表明，富含碳水合物的餐会显着加剧盆中的前症状症状， 但是，解释这种临床观察的基本机制仍然未知。 彼此之间，我们的小组进行了一项初步研究，以评估POTS过剩的病理生理学 葡萄糖摄入后的体位心动过速；我们调查了血液动力学和神经激素的变化 发生在锅患者的75 gr口服葡萄糖挑战（餐后期）和健康状态后发生的。 控件。与禁食条件相比，葡萄糖的摄入使盆中的直立心动过速恶化 患者，与健康相比，这与直立中风量的减少更加可靠 控件。关于POTS患者的直立中风量的不成比例减少，这可能是，这可能是， 在某种程度上，通过模式循环中的大量血液集合来解释。原理循环是 人体最大的血液体积储层，占总血液量的约25％。站立， 有大量的血液聚集，主要发生在方案静脉中。最后，我们的研究也有 表明摄入75-gr葡萄糖后30分钟后，POTS患者的分泌有选择性增加 与健康对照组相比，葡萄糖依赖性胰岛素多肽（GIP）激素的含量。这 Horseone在Schemechnic圆圈中具有血管舒张特性。重要的是，GIP分泌的增加 在盆中葡萄糖摄入后，时间依赖于时间依赖性。 因此，这些发现表明GIP在增加的病理生理学中的潜在贡献 植物后体位心动过速和盆前患者的同步症状。因此， 该建议是调查定位心动过速加重的基础机制和 花盆响应葡萄糖摄入的盆前症状。具体来说，我们将评估贡献 口服葡萄糖和直立姿势的静态静脉电容的变化的GIP POTS患者。