Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Separation
  • Cholecystokinin / metabolism
  • Chromogranin A / metabolism
  • Enteroendocrine Cells / cytology*
  • Flow Cytometry / methods*
  • Gene Expression Profiling*
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / metabolism
  • Intestines / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis
  • Peptides / chemistry
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • Chromogranin A
  • Peptides
  • Transcription Factors
  • Cholecystokinin