Zhou June, Martin Roy J, Tulley Richard T, Raggio Anne M, McCutcheon Kathleen L, Shen Li, Danna Samuel Colby, Tripathy Sasmita, Hegsted Maren, Keenan Michael J
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1160-6. doi: 10.1152/ajpendo.90637.2008. Epub 2008 Sep 16.
Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are anti-diabetes/obesity hormones secreted from the gut after meal ingestion. We have shown that dietary-resistant starch (RS) increased GLP-1 and PYY secretion, but the mechanism remains unknown. RS is a fermentable fiber that lowers the glycemic index of the diet and liberates short-chain fatty acids (SCFAs) through fermentation in the gut. This study investigates the two possible mechanisms by which RS stimulates GLP-1 and PYY secretion: the effect of a meal or glycemic index, and the effect of fermentation. Because GLP-1 and PYY secretions are stimulated by nutrient availability in the gut, the timing of blood sample collections could influence the outcome when two diets with different glycemic indexes are compared. Thus we examined GLP-1 and PYY plasma levels at various time points over a 24-h period in RS-fed rats. In addition, we tested proglucagon (a precursor to GLP-1) and PYY gene expression patterns in specific areas of the gut of RS-fed rats and in an enteroendocrine cell line following exposure to SCFAs in vitro. Our findings are as follows. 1) RS stimulates GLP-1 and PYY secretion in a substantial day-long manner, independent of meal effect or changes in dietary glycemia. 2) Fermentation and the liberation of SCFAs in the lower gut are associated with increased proglucagon and PYY gene expression. 3) Glucose tolerance, an indicator of increased active forms of GLP-1 and PYY, was improved in RS-fed diabetic mice. We conclude that fermentation of RS is most likely the primary mechanism for increased endogenous secretions of total GLP-1 and PYY in rodents. Thus any factor that affects fermentation should be considered when dietary fermentable fiber is used to stimulate GLP-1 and PYY secretion.
胰高血糖素样肽-1（GLP-1）和肽YY（PYY）是进食后从肠道分泌的抗糖尿病/肥胖激素。我们已经表明，膳食抗性淀粉（RS）可增加GLP-1和PYY的分泌，但其机制尚不清楚。RS是一种可发酵纤维，可降低饮食的血糖指数，并通过肠道发酵释放短链脂肪酸（SCFA）。本研究调查了RS刺激GLP-1和PYY分泌的两种可能机制：膳食或血糖指数的影响以及发酵的影响。由于GLP-1和PYY的分泌受到肠道中营养物质可用性的刺激，因此在比较两种血糖指数不同的饮食时，采血时间可能会影响结果。因此，我们在RS喂养的大鼠中，在24小时内的不同时间点检测了GLP-1和PYY的血浆水平。此外，我们测试了RS喂养的大鼠肠道特定区域以及体外暴露于SCFA后的肠内分泌细胞系中胰高血糖素原（GLP-1的前体）和PYY的基因表达模式。我们的研究结果如下。1）RS以显著的全天方式刺激GLP-1和PYY的分泌，与膳食效应或饮食血糖变化无关。2）下肠道中SCFA的发酵和释放与胰高血糖素原和PYY基因表达的增加有关。3）在RS喂养的糖尿病小鼠中，葡萄糖耐量（GLP-1和PYY活性形式增加的指标）得到改善。我们得出结论，RS的发酵很可能是啮齿动物中总GLP-1和PYY内源性分泌增加的主要机制。因此，当使用膳食可发酵纤维来刺激GLP-1和PYY分泌时，应考虑任何影响发酵的因素。
