Abstract

Enterochromaffin (EC) cells located in the gastrointestinal (GI) tract provide the vast majority of serotonin (5‐HT) in the body and constitute half of all enteroendocrine cells. EC cells respond to an array of stimuli, including various ingested nutrients. Ensuing 5‐HT release from these cells plays a diverse role in regulating gut motility as well as other important responses to nutrient ingestion such as glucose absorption and fluid balance. Recent data also highlight the role of peripheral 5‐HT in various pathways related to metabolic control. Details related to the manner by which EC cells respond to ingested nutrients are scarce and as that the nutrient environment changes along the length of the gut, it is unknown whether the response of EC cells to nutrients is dependent on their GI location. The aim of the present study was to identify whether regional differences in nutrient sensing capability exist in mouse EC cells. We isolated mouse EC cells from duodenum and colon to demonstrate differential responses to sugars depending on location. Measurements of intracellular calcium concentration and 5‐HT secretion demonstrated that colonic EC cells are more sensitive to glucose, while duodenal EC cells are more sensitive to fructose and sucrose. Short‐chain fatty acids (SCFAs), which are predominantly synthesized by intestinal bacteria, have been previously associated with an increase in circulating 5‐HT; however, we find that SCFAs do not acutely stimulate EC cell 5‐HT release. Thus, we highlight that EC cell physiology is dictated by regional location within the GI tract, and identify differences in the regional responsiveness of EC cells to dietary sugars.

Highlights

  • Enteroendocrine (EE) cells are specialized epithelial cells within the gastrointestinal (GI) tract equipped to release an array of hormones and peptides in response to environmental cues

  • Stimulation of duodenal EC cells with 100 mmol/L glucose caused a sustained reduction in Ca2+(i) compared to prestimulation baseline (Fig 1A), resulting in a negative total net flux compared to the unstimulated control (AUC P < 0.01, Fig. 1B)

  • In order to relate these findings to 5-HT secretion, 5-HT release was determined by immunoassay. 5-HT release from duodenal

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Summary

Introduction

Enteroendocrine (EE) cells are specialized epithelial cells within the gastrointestinal (GI) tract equipped to release an array of hormones and peptides in response to environmental cues. They constitute the largest endocrine tissue in our body. Enterochromaffin (EC) cells represent around half of all EE cells, and produce ~95% of total body serotonin (5-hydroxytryptophan, 5-HT), including all plasma 5-HT (Gershon and Tack 2007). These are endoderm-derived cells that express the nonneuronal isoform of tryptophan hydroxylase, TPH1. Much research has focused on roles of gut-derived 5-HT within the GI tract, including our own work proving that GI motility is regulated by gut-derived 5-HT but can be maintained without it (Keating and Spencer 2010; Spencer et al 2011).

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