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: 10522696
• 负责人: Cyndya Adriana Shibao
• 金额: $ 80.65万
• 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/10522696
• 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; base; 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.

项目概要 姿势性心动过速综合征 (POTS) 影响着美国约 300 万成年人。 由于站立时发生的慢性晕厥前症状和心动过速，生活质量较差。 研究表明，富含碳水化合物的膳食会显着加剧 POTS 患者的晕厥前症状， 然而，解释这一临床观察结果的根本机制仍然未知。 因此，我们小组进行了一项初步研究来评估 POTS 过度的病理生理学 摄入葡萄糖后出现直立性心动过速；我们调查了血流动力学和神经激素的变化 POTS 患者和健康人在接受 75 克口服葡萄糖挑战长达 2 小时（餐后）后发生 与禁食条件相比，摄入葡萄糖加速了 POTS 中的直立性心动过速。 与健康人相比，这与直立每搏输出量更大幅度减少有关 就 POTS 患者的直立每搏输出量不成比例地减少而言，这可能是： 部分原因是内脏循环中的大量血液聚集。 人体最大的血容量，站立时储存约25%的血容量。 存在显着的血液汇集，主要发生在内脏静脉中。最后，我们的研究也发现了这一点。 结果表明，摄入 75 克葡萄糖 30 分钟后，POTS 患者的分泌量选择性增加 与健康对照相比，葡萄糖依赖性促胰岛素多肽（GIP）激素的变化。 激素在内脏循环中具有血管舒张作用，重要的是，GIP 分泌增加。 与 POTS 摄入葡萄糖后直立每搏输出量的下降呈时间依赖性相关。 经过检查，这些发现指出了 GIP 在增加的病理生理学中的潜在贡献 POTS 患者的餐后直立性心动过速和晕厥前症状因此，总体目标是。 该提案旨在研究直立性心动过速恶化的机制 具体来说，我们将评估对葡萄糖摄入的反应的晕厥前症状。 GIP对口服葡萄糖后和直立姿势期间内脏静脉电容变化的影响 POTS 患者。