Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Addenbrooke's Hospital, Box 139, Hills Road, Cambridge, CB2 0XY, United Kingdom.
Endocrinology. 2012 Jul;153(7):3054-65. doi: 10.1210/en.2011-2170. Epub 2012 Jun 8.
The intestine secretes a range of hormones with important local and distant actions, including the control of insulin secretion and appetite. A number of enteroendocrine cell types have been described, each characterized by a distinct hormonal signature, such as K-cells producing glucose-dependent insulinotropic polypeptide (GIP), L-cells producing glucagon-like peptide-1 (GLP-1), and I-cells producing cholecystokinin (CCK). To evaluate similarities between L-, K-, and other enteroendocrine cells, primary murine L- and K-cells, and pancreatic α- and β-cells, were purified and analyzed by flow cytometry and microarray-based transcriptomics. By microarray expression profiling, L cells from the upper small intestinal (SI) more closely resembled upper SI K-cells than colonic L-cells. Upper SI L-cell populations expressed message for hormones classically localized to different enteroendocrine cell types, including GIP, CCK, secretin, and neurotensin. By immunostaining and fluorescence-activated cell sorting analysis, most colonic L-cells contained GLP-1 and PeptideYY In the upper SI, most L-cells contained CCK, approximately 10% were GIP positive, and about 20% were PeptideYY positive. Upper SI K-cells exhibited approximately 10% overlap with GLP-1 and 6% overlap with somatostatin. Enteroendocrine-specific transcription factors were identified from the microarrays, of which very few differed between the enteroendocrine cell populations. Etv1, Prox1, and Pax4 were significantly enriched in L-cells vs. K cells by quantitative RT-PCR. In summary, our data indicate a strong overlap between upper SI L-, K-, and I-cells and suggest they may rather comprise a single cell type, within which individual cells exhibit a hormonal spectrum that may reflect factors such as location along the intestine and exposure to dietary nutrients.
肠道分泌一系列具有重要局部和远处作用的激素，包括胰岛素分泌和食欲的控制。已经描述了许多肠内分泌细胞类型，每种类型都具有独特的激素特征，例如产生葡萄糖依赖性胰岛素释放肽 (GIP) 的 K 细胞、产生胰高血糖素样肽-1 (GLP-1) 的 L 细胞和产生胆囊收缩素 (CCK) 的 I 细胞。为了评估 L 细胞、K 细胞和其他肠内分泌细胞之间的相似性，纯化了原代小鼠 L 细胞和 K 细胞以及胰腺 α 细胞和 β 细胞，并通过流式细胞术和基于微阵列的转录组学进行了分析。通过微阵列表达谱分析，来自小肠上部 (SI) 的 L 细胞比结肠 L 细胞更类似于上 SI 的 K 细胞。上 SI L 细胞群体表达了经典定位于不同肠内分泌细胞类型的激素的信息，包括 GIP、CCK、分泌素和神经降压素。通过免疫染色和荧光激活细胞分选分析，大多数结肠 L 细胞含有 GLP-1 和 PYY。在上 SI，大多数 L 细胞含有 CCK，约 10%是 GIP 阳性，约 20%是 PYY 阳性。上 SI K 细胞与 GLP-1 有大约 10%的重叠，与生长抑素有 6%的重叠。从微阵列中鉴定出肠内分泌细胞特异性转录因子，其中很少有在肠内分泌细胞群体之间存在差异。通过定量 RT-PCR，Etv1、Prox1 和 Pax4 在 L 细胞中明显比 K 细胞丰富。总之，我们的数据表明上 SI 的 L 细胞、K 细胞和 I 细胞之间存在很强的重叠，并表明它们可能组成一个单一的细胞类型，其中单个细胞表现出的激素谱可能反映了位置沿肠道和暴露于饮食营养素等因素。
