Department of Biomedical Sciences, NNF Centre for Basic Metabolic Research, the Panum Institute, University of Copenhagen, Copenhagen, Denmark;
Am J Physiol Gastrointest Liver Physiol. 2014 Apr 1;306(7):G622-30. doi: 10.1152/ajpgi.00372.2013. Epub 2014 Feb 13.
Nutrients often stimulate gut hormone secretion, but the effects of fructose are incompletely understood. We studied the effects of fructose on a number of gut hormones with particular focus on glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In healthy humans, fructose intake caused a rise in blood glucose and plasma insulin and GLP-1, albeit to a lower degree than isocaloric glucose. Cholecystokinin secretion was stimulated similarly by both carbohydrates, but neither peptide YY3-36 nor glucagon secretion was affected by either treatment. Remarkably, while glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might be useful targets for type 2 diabetes mellitus and obesity drug development.
营养素通常会刺激肠道激素分泌，但果糖的作用尚不完全清楚。我们研究了果糖对多种肠道激素的影响，特别关注胰高血糖素样肽 1（GLP-1）和葡萄糖依赖性胰岛素释放肽（GIP）。在健康人群中，果糖摄入会导致血糖和血浆胰岛素以及 GLP-1 升高，尽管其升高幅度低于等热量的葡萄糖。两种碳水化合物均能刺激胆囊收缩素分泌，但两种肽 YY3-36 和胰高血糖素的分泌均不受任何一种处理的影响。值得注意的是，虽然葡萄糖能强烈刺激 GIP 释放，但果糖却没有效果。在小鼠和大鼠中也发现了类似的模式，果糖和葡萄糖均能刺激 GLP-1 分泌，而只有葡萄糖能引起 GIP 分泌。在 GLUTag 细胞中，果糖被代谢并通过 ATP 敏感性钾通道关闭和细胞去极化以剂量依赖的方式刺激 GLP-1 分泌（EC50 = 0.155 mM），GLUTag 细胞是用于 L 细胞的小鼠细胞系。由于果糖在刺激 GLP-1 分泌时不会同时释放促胰高血糖素的 GIP，因此果糖刺激 GLP-1 释放的途径可能是 2 型糖尿病和肥胖症药物开发的有用靶点。
