Sugar Responses of Human Enterochromaffin Cells Depend on Gut Region, Sex, and Body Mass.

Amanda Lumsden,Richard Young,Nam Nguyen,David Wattchow,Christopher Rayner,Steven Due,Nicole Isaacs,Emily Sun,Dayan De Fontgalland,V Jackson,Nektaria Pezos,Alice Liou,Damien Keating,Luigi Sposato,Gudrun Schober,Philippa Rabbitt,Paul Hollington,Alyce Martin

doi:10.3390/nu11020234

Abstract

Gut-derived serotonin (5-HT) is released from enterochromaffin (EC) cells in response to nutrient cues, and acts to slow gastric emptying and modulate gastric motility. Rodent studies also evidence a role for gut-derived 5-HT in the control of hepatic glucose production, lipolysis and thermogenesis, and in mediating diet-induced obesity. EC cell number and 5-HT content is increased in the small intestine of obese rodents and human, however, it is unknown whether EC cells respond directly to glucose in humans, and whether their capacity to release 5-HT is perturbed in obesity. We therefore investigated 5-HT release from human duodenal and colonic EC cells in response to glucose, sucrose, fructose and α-glucoside (αMG) in relation to body mass index (BMI). EC cells released 5-HT only in response to 100 and 300 mM glucose (duodenum) and 300 mM glucose (colon), independently of osmolarity. Duodenal, but not colonic, EC cells also released 5-HT in response to sucrose and αMG, but did not respond to fructose. 5-HT content was similar in all EC cells in males, and colonic EC cells in females, but 3 to 4-fold higher in duodenal EC cells from overweight females (p < 0.05 compared to lean, obese). Glucose-evoked 5-HT release was 3-fold higher in the duodenum of overweight females (p < 0.05, compared to obese), but absent here in overweight males. Our data demonstrate that primary human EC cells respond directly to dietary glucose cues, with regional differences in selectivity for other sugars. Augmented glucose-evoked 5-HT release from duodenal EC is a feature of overweight females, and may be an early determinant of obesity.

Highlights

Serotonin (5-hydroxytryptamine; 5-HT) is a monoamine produced from the hydroxylation of the dietary amino acid L-tryptophan via the rate-limiting actions of tryptophan hydroxylase (TPH).In vertebrates, two isoforms of TPH are encoded by the genes TPH1 and TPH2, and give rise to independent pools of 5-HT
EC cells were exposed to euglycemic 5 mM, dependent manner at meal-related 100 mM (p < 0.05) and 300 mM glucose concentrations (p < 0.01), hyperglycaemic 30 mM, and meal-related 100 mM or 300 mM glucose concentrations while 5-HT was released from colonic EC cells at 300 mM glucose (p < 0.001, Figure 1)
Duodenal EC cells released 5-HT in response was observed in 30 mM glucose (Figure 1)

Summary

Introduction

Serotonin (5-hydroxytryptamine; 5-HT) is a monoamine produced from the hydroxylation of the dietary amino acid L-tryptophan via the rate-limiting actions of tryptophan hydroxylase (TPH).In vertebrates, two isoforms of TPH are encoded by the genes TPH1 and TPH2, and give rise to independent pools of 5-HT. Serotonin (5-hydroxytryptamine; 5-HT) is a monoamine produced from the hydroxylation of the dietary amino acid L-tryptophan via the rate-limiting actions of tryptophan hydroxylase (TPH). TPH1 is expressed in the periphery, largely in enterochromaffin (EC) cells of the gastrointestinal (GI) tract [1,2] where the majority (~90%) of total body 5-HT is produced [3]. TPH2 is expressed largely in neurons of the myenteric plexus, and centrally in the Raphe nuclei of the brainstem [2]. Free (extracellular) 5-HT can be transported into cells expressing the serotonin transporter (SERT). In the liver, this reuptake precedes breakdown of 5-HT to the metabolite 5-hydroxyindoleacetic acid (5-HIAA), which is excreted via the kidney

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