Can encapsulated glutamine increase GLP-1 secretion, improve glucose tolerance, and reduce meal size in healthy volunteers? A randomised, placebo-controlled, cross-over trial.
Can encapsulated glutamine increase GLP-1 secretion, improve glucose tolerance, and reduce meal size in healthy volunteers? A randomised, placebo-controlled, cross-over trial.
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DOI：
10.1016/s0140-6736(15)60383-x
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发表时间：
2015-02-26
期刊：
影响因子：
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通讯作者：
Gribble, Fiona M
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作者：
Meek, Claire L;Reimann, Frank;Gribble, Fiona M
背景：肥胖是全球关注的问题，可以通过昂贵且有创的减肥手术有效治疗。手术后体重减轻是由于营养物质输送到小肠下部，同时释放促饱腹感的肠道激素，如胰高血糖素样肽1 （GLP-1）。我们的目的是评估谷氨酰胺，一种体内GLP-1的有效分泌剂，是否增加GLP-1的释放，改善葡萄糖耐量，或减少志愿者的食量。方法：在英国剑桥进行了一项单中心、随机、双盲、安慰剂对照的交叉研究，研究了单剂量胶囊化回肠释放谷氨酰胺（6 g）和安慰剂（微晶纤维素）对健康成人志愿者的影响。每个终点招募志愿者，并按随机顺序接受每个方案（通过电子随机数生成进行）。主要终点是人体内静脉血GLP-1（浓度和曲线下面积）。次要结果是葡萄糖耐量（90分钟后口服葡萄糖耐量试验测量）和餐量（120分钟后随意用餐）。每个终点纳入8-10名参与者将获得90%的功效，alpha值为0.05。显著性检验采用配对t检验。参与者给予书面知情同意，该研究由当地研究伦理委员会批准。本试验已在ISRCTN注册，注册号为ISRCTN10757078。结果：招募了11名男性和13名女性（年龄22-58岁，体重指数18.5 - 31.8 kg/m(2)）。10例患者进行GLP-1评估，8例进行葡萄糖耐量评估，10例进行餐量评估。一些志愿者参与了研究的多个部分。与安慰剂相比，摄入6 g谷氨酰胺与90分钟后GLP-1浓度升高相关（平均3.2 pmol/L [SD 0.86]对2.1 pmol/L [0.65], p= 0.004），与90分钟后胰岛素浓度升高相关（70·9[37·9]对51·5[23·1]，p= 0.048），与120分钟时食量增加相关（摄入542 g[188]对481 [193]，p= 0.008）。摄入谷氨酰胺后没有发现安全问题。解释：该试验表明单次口服谷氨酰胺胶囊可促进GLP-1分泌增加，并与胰岛素释放增加相关。然而，效应量很小，不太可能在临床上有用。谷氨酰胺与餐量增加有关，这是一种不良效应，可能是因为胰岛素释放的厌氧效应大于谷氨酰胺给药后GLP-1释放的厌氧效应。资助：欧洲联盟第七个框架方案、威康信托基金会转化医学和治疗方案、国家卫生研究所。
BACKGROUND: Obesity is a global concern and can be effectively treated with bariatric surgery, which is expensive and invasive. Weight loss after surgery has been attributed to increased nutrient delivery to the lower small intestine with release of satiety-promoting gut hormones such as glucagon-like peptide 1 (GLP-1). We aimed to assess whether glutamine, a potent secretagogue of GLP-1 in vivo, increases GLP-1 release, improves glucose tolerance, or reduces meal size in volunteers.METHODS: A single-centre, randomised, double blind, placebo-controlled, cross-over study was performed in Cambridge, UK, studying the effects of a single dose of encapsulated ileal-release glutamine (6 g) and placebo (microcrystalline cellulose) in healthy adult volunteers. Volunteers were recruited for each endpoint and received each regimen in random order (performed by electronic random number generation). The primary outcome was within-person GLP-1 in venous blood (concentrations and area under the curve). Secondary outcomes were glucose tolerance (measured with an oral glucose tolerance test given after 90 min) and meal size (ad-libitum meal given at 120 min). Inclusion of 8-10 participants for each endpoint would achieve 90% power with alpha at 0·05. Significance testing was done with the paired t test. Participants gave written informed consent and the study was approved by the local research ethics committee. This trial is registered with the ISRCTN register, number ISRCTN10757078.FINDINGS: 11 men and 13 women were recruited (aged 22-58 years, body-mass index 18·5-31·8 kg/m(2)). Ten patients were assigned to assessment of GLP-1, eight to assessment of glucose tolerance, and ten for meal size. Some volunteers participated in more than one part of the study. Ingestion of 6 g glutamine was associated with increased GLP-1 concentrations after 90 min compared with placebo (mean 3·2 pmol/L [SD 0·86] vs 2·1 [0·65], p=0·004), increased insulin concentrations after 90 min (70·9 [37·9] vs 51·5 [23·1], p=0·048), and increased meal size at 120 min (542 g eaten [188] vs 481 [193], p=0·008). No safety concerns were identified after the ingestion of glutamine.INTERPRETATION: This trial shows that a single oral dose of encapsulated glutamine can promote increased secretion of GLP-1 and is associated with increased insulin release. However, the effect size was small and unlikely to be clinically useful. Glutamine was associated with increased meal size, an undesirable effect, perhaps because the orexigenic effects of insulin release predominated over the anorexigenic effects of GLP-1 release after administration of glutamine.FUNDING: European Union's Seventh Framework Programme, Wellcome Trust Translational Medicine & Therapeutics Programme, National Institute for Health Research.