Overlap of Endocrine Hormone Expression in the Mouse Intestine Revealed by Transcriptional Profiling and Flow Cytometry

被引:306
作者
Habib, Abdella M. [1 ]
Richards, Paul [1 ]
Cairns, Lynne S. [1 ]
Rogers, Gareth J. [1 ]
Bannon, Christopher A. M. [1 ]
Parker, Helen E. [1 ]
Morley, Tom C. E. [1 ]
Yeo, Giles S. H. [2 ]
Reimann, Frank [1 ]
Gribble, Fiona M. [1 ]
机构
[1] Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England
[2] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
GLUCAGON-LIKE PEPTIDE-1; DEPENDENT INSULINOTROPIC POLYPEPTIDE; PANCREATIC BETA-CELLS; GASTROINTESTINAL-TRACT; ENTEROENDOCRINE CELLS; GLUCOSE; GIP; DIFFERENTIATION; GLP-1; LINE;
D O I
10.1210/en.2011-2170
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 alpha- and beta-cells, were purified and analyzed by flow cytometry and microarray-based transcriptomics. By microarray expression profiling, L cells from the upper small intestinal (SI) moreclosely 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. (Endocrinology 153: 3054-3065, 2012)
引用
收藏
页码:3054 / 3065
页数:12
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