The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin
Open accessAbstract
Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.
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Cites
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“A series of reports on transgenic reporter mice expressing variants of GFP under the control of promoters for different gut peptide precursors have been published over the last couple of years without mention of coexpression of nonexpected peptide hormones (23, 28, 36, 37).”
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Self-citation
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Single-cell messenger RNA sequencing reveals rare intestinal cell types
Grün, D., Lyubimova, A., Kester, L., Wiebrands, K., Basak, O., Sasaki, N., Clevers, H., & van Oudenaarden, A. (2015) · Nature · doi:10.1038/nature14966 · Cited by 1,234
Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium
Gribble, F. M., & Reimann, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105439 · Cited by 683
Function and mechanisms of enteroendocrine cells and gut hormones in metabolism
Gribble, F. M., & Reimann, F. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0168-8 · Cited by 670
Steinert, R. E., Feinle-Bisset, C., Asarian, L., Horowitz, M., Beglinger, C., & Geary, N. (2017) · Physiological Reviews · doi:10.1152/physrev.00031.2014 · Cited by 578
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Metadata
- Authors
- Egerod, K. L., Engelstoft, M. S., Grunddal, K. V., Nøhr, M. K., Secher, A., Sakata, I., Pedersen, J., Windeløv, J. A., Füchtbauer, E.-M., Olsen, J., Sundler, F., Christensen, J. P., Wierup, N., Olsen, J. V., Holst, J. J., Zigman, J. M., Poulsen, S. S., & Schwartz, T. W.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-12-01
- Volume
- 153
- Issue
- 12
- Pages
- 5782-5795
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2062423798
- Cited by
- 334
- References
- 45
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Egerod, K. L., Engelstoft, M. S., Grunddal, K. V., Nøhr, M. K., Secher, A., Sakata, I., Pedersen, J., Windeløv, J. A., Füchtbauer, E.-M., Olsen, J., Sundler, F., Christensen, J. P., Wierup, N., Olsen, J. V., Holst, J. J., Zigman, J. M., Poulsen, S. S., & Schwartz, T. W. (2012). A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin. Endocrinology. https://doi.org/10.1210/en.2012-1595
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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