背景:在人类中,十二指肠内输注L-色氨酸(Trp)可增加胃肠激素的血浆浓度并刺激幽门压,既是胃排空的关键决定因素,也与能量摄入的有效抑制有关。已经显示了Trp对胃肠激素的刺激,在临床前研究中,被细胞外钙增强,部分由钙敏感受体介导。
目的:确定十二指肠内钙是否可以增强Trp刺激胃肠激素和幽门压力的作用,如果是这样,是否与更大的能量摄入抑制有关,在健康的男性。
方法:15名体重正常的男性(平均±SD;年龄:26±7岁;体重指数:22±2kg/m2),在三个不同的场合收到,150分钟的十二指肠内输注0、500或1000毫克钙(Ca),每个结合Trp(负载:0.1kcal/min,在t=75-150分钟的次最大能量摄入抑制效应下),在一个随机的,双盲,交叉研究。胃肠激素的血浆浓度(胃泌素,胆囊收缩素,葡萄糖依赖性促胰岛素多肽(GIP),胰高血糖素样肽-1(GLP-1),肽酪氨酸-酪氨酸(PYY),Trp,并在整个过程中测量了横十二指肠压力。输注后立即(t=150-180分钟),对标准自助餐中的能量摄入进行了量化.
结果:单独对钙的反应,500毫克和1000毫克的剂量刺激PYY,而仅1000mg剂量刺激GLP-1和幽门压(均P<0.05)。1000毫克剂量还增强了Trp刺激胆囊收缩素和GLP-1的作用,并且两个剂量都刺激了PYY,但是,令人惊讶的是,GIP的刺激降低(均P<0.05)。两种剂量均显著和剂量依赖性地增强了Trp抑制能量摄入的作用(kcal;Ca-0+Trp:1108±70,Ca-500+Trp:961±90,Ca-1000+Trp:922±96;P<0.05)。
结论:十二指肠内给予钙可增强Trp刺激血浆胆囊收缩素的作用,GLP-1和PYY,抑制能量摄入,在健康。这些发现对肥胖中基于营养的新型能量摄入调节方法具有潜在意义。
背景:该试验已在澳大利亚新西兰临床试验注册中心注册(www.anzctr.org.au;试验编号:ACTRN12620001294943)。
BACKGROUND: In humans, intraduodenal infusion of L-tryptophan (Trp) increases plasma concentrations of gastrointestinal hormones and stimulates pyloric pressures, both key determinants of gastric emptying and associated with potent suppression of energy intake. The stimulation of gastrointestinal hormones by Trp has been shown, in preclinical studies, to be enhanced by extracellular calcium and mediated in part by the calcium-sensing receptor.
OBJECTIVE: This study aim was to determine whether intraduodenal calcium can enhance the effects of Trp to stimulate gastrointestinal hormones and pyloric pressures and, if so, whether it is associated with greater suppression of energy intake, in healthy males.
METHODS: Fifteen males with normal weight (mean ± standard deviation; age: 26 ± 7 years; body mass index: 22 ± 2 kg/m2), received on 3 separate occasions, 150-min intraduodenal infusions of 0, 500, or 1000 mg calcium (Ca), each combined with Trp (load: 0.1 kcal/min, with submaximal energy intake-suppressant effects) from t = 75-150 min, in a randomized, double-blind, crossover study. Plasma concentrations of GI hormones [gastrin, cholecystokinin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide (GLP)-1, and peptide tyrosine-tyrosine (PYY)], and Trp and antropyloroduodenal pressures were measured throughout. Immediately postinfusions (t = 150-180 min), energy intake at a standardized buffet-style meal was quantified.
RESULTS: In response to calcium alone, both 500- and 1000-mg doses stimulated PYY, while only the 1000-mg dose stimulated GLP-1 and pyloric pressures (all P < 0.05). The 1000-mg dose also enhanced the effects of Trp to stimulate cholecystokinin and GLP-1, and both doses stimulated PYY but, surprisingly, reduced the stimulation of GIP (all P < 0.05). Both doses substantially and dose dependently enhanced the effects of Trp to suppress energy intake (Ca-0+Trp: 1108 ± 70 kcal; Ca-500+Trp: 961 ± 90 kcal; and Ca-1000+Trp: 922 ± 96 kcal; P < 0.05).
CONCLUSIONS: Intraduodenal administration of calcium enhances the effect of Trp to stimulate plasma cholecystokinin, GLP-1, and PYY and suppress energy intake in healthy males. These findings have potential implications for novel nutrient-based approaches to energy intake regulation in obesity. The trial was registered at the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12620001294943).