Quantitation and chemical coding of enteroendocrine cell populations in the human jejunum
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Recent studies reveal substantial species and regional differences in enteroendocrine cell (EEC) populations, including differences in patterns of hormone coexpression, which limit extrapolation between animal models and human. In this study, jejunal samples, with no histologically identifiable pathology, from patients undergoing Whipple’s procedure were investigated for the presence of gastrointestinal hormones using double- and triple-labelling immunohistochemistry and high-resolution confocal microscopy. Ten hormones (5-HT, CCK, secretin, proglucagon-derived peptides, PYY, GIP, somatostatin, neurotensin, ghrelin and motilin) were localised in EEC of the human jejunum. If only single staining is considered, the most numerous EEC were those containing 5-HT, CCK, ghrelin, GIP, motilin, secretin and proglucagon-derived peptides. All hormones had some degree of colocalisation with other hormones. This included a population of EEC in which GIP, CCK and proglucagon-derived peptides are costored, and four 5-HT cell populations, 5-HT/GIP, 5-HT/ghrelin, 5-HT/PYY, and 5-HT/secretin cell groups, and a high degree of overlap between motilin and ghrelin. The presence of 5-HT in many secretin cells is consistent across species, whereas lack of 5-HT and CCK colocalisation distinguishes human from mouse. It seems likely that the different subclasses of 5-HT cells subserve different roles. At a subcellular level, we examined the vesicular localisation of secretin and 5-HT, and found these to be separately stored. We conclude that hormone-containing cells in the human jejunum do not comply with a one-cell, one-hormone classification and that colocalisations of hormones are likely to define subtypes of EEC that have different roles.
KeywordsEnteroendocrine cells Gastrointestinal hormones 5-Hydroxytryptamine Cholecystokinin Glucose-dependent insulinotropic peptide
This work was supported by NIH (SPARC) grant ID # OT2OD023847 (PI Terry Powley) to JBF. We thank Josiane Fakhry for helpful comments on the manuscript. Confocal imaging was performed at the Biological Optical Microscopy Platform, University of Melbourne.
NIH (SPARC) grant ID # OT2OD023847 (PI Terry Powley) to JBF.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
Informed consent was obtained.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Procedures were approved by the Human Research Ethics Committee of Austin Health
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