Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial
Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial
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DOI：
10.1152/ajpgi.00371.2019
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发表时间：
2020-04-01
影响因子：
4.5
通讯作者：
Camilleri, Michael
中科院分区：
文献类型：
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作者：
Brandler, Justin;Miller, Laurence J.;Camilleri, Michael
胃调节（GA）和胃排空异常导致功能性消化不良（FD）的病理生理学。在动物研究中促胰液素是 GA 的关键调节因子。我们的目的是研究促胰液素对胃动力、饱腹感、餐后症状和关键激素的影响。我们对 10 名健康志愿者和 10 名符合罗马 IV 标准的 FD 患者进行了两项双盲、随机、盐水对照交叉试验。我们在 In-111 放射性标记 Ensure 300 mL 膳食后使用测量的 GA（通过经过验证的 SPECT 方法），并通过闪烁扫描量化胃排空 30 分钟。通过 Ensure 营养饮料测试中的饱足量 (VTF) 和最大耐受量 (MTV) 以及 MTV 后 30 分钟的餐后症状来测量饱腹感。测量空腹和餐后 GLP-1、GIP 和 HPP。健康对照者和 FD 患者的年龄和性别分布相似。与安慰剂相比，促胰液素在健康者中延迟 30 分钟胃排空[-11% (-16, -4), P = 0.004]；和 FD [-8% (-9, 0), P = 0.03]。健康或 FD 治疗组之间的饱腹感（VTF 和 MTV）、GA 以及血浆 GLP-1、GIP 和 HPP 水平没有差异。根据 ANCOVA 分析（根据年龄和性别进行调整），促胰液素并未始终增加健康或 FD 的餐后症状。促胰液素延迟健康和 FD 中的胃排空，而不会显着改变 GA、VTF 或 MTV 或选定的激素。因此，促胰液素受体激活可能为 FD 和胃排空过快的患者提供一种新的治疗机制。新的和值得注意的天然激素促胰液素可延迟胃固体排空，而不会对胃调节、饱腹感、其他上消化道激素或餐后症状产生有害影响。鉴于这些发现，一部分胃快速排空的患者（例如，估计有 20% 的功能性消化不良患者）可能适合接受刺激促胰液素受体的治疗，例如沙库巴曲，它能抑制脑啡肽酶（一种降解促胰液素的酶）。
Abnormal gastric accommodation (GA) and gastric emptying contribute to pathophysiology in functional dyspepsia (FD). Secretin is a key regulator of GA in animal studies. Our aim was to study the effects of secretin on gastric motility, satiation, postprandial symptoms, and key hormones. We performed two double-blind, randomized, saline-controlled crossover trials in 10 healthy volunteers and 10 patients with FD by Rome IV criteria. We used measured GA (by validated SPECT method) after a In-111 radiolabeled Ensure 300-mL meal and quantified gastric emptying for 30 min by scintigraphy. Satiation was measured by volume to fullness (VTF) and maximum tolerated volume (MTV) on an Ensure nutrient drink test and postprandial symptoms 30 min post-MTV. Fasting and postprandial GLP-1, GIP, and HPP were measured. The ages and sex distribution of healthy controls and patients with FD were similar. Compared with placebo, secretin delayed gastric emptying at 30 min in both health [-11% (-16, -4), P = 0.004]; and FD [-8% (-9, 0), P = 0.03]. Satiation (VTF and MTV), GA, and plasma levels of GLP-1, GIP, and HPP did not differ between treatment arms in health or FD. On ANCOVA analysis (adjusting for age and sex), secretin did not consistently increase postprandial symptoms in health or FD. Secretin delayed gastric emptying in both health and FD without significantly altering GA, VTF, or MTV or selected hormones. Thus, secretin receptor activation may provide a novel therapeutic mechanism for patients with FD and rapid gastric emptying.NEW & NOTEWORTHY The naturally occurring hormone secretin retards gastric emptying of solids without deleteriously affecting gastric accommodation, satiation, other upper gastrointestinal hormones, or postprandial symptoms. Given these findings, a subset of patients with rapid gastric emptying (e.g., the estimated 20% of patients with functional dyspepsia) could be candidates for treatments that stimulate a secretin receptor such as sacubitril, which inhibits neprilysin, an enzyme that degrades secretin.