Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

Ma, Jing; Bellon, Max; Wishart, Judith M.; Young, Richard L.; Blackshaw, L. Ashley; Jones, Karen L.; Rayner, Christopher K.

doi:10.1152/ajpgi.90708.2008

Cited by 218 publications

(192 citation statements)

References 48 publications

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“…Our data are in accord with recently published human data (Ma et al, 2009) and in vivo rat data (Fujita et al, 2009), in which sucralose ingestion failed to stimulate a rise in two circulating incretin hormones, GLP-1 and the K cell-derived glucose-dependent insulinotropic polypeptide. Ma et al administered sucralose nasogastrically to healthy, normalweight volunteers and observed no effect on plasma GLP-1 or glucose-dependent insulinotropic polypeptide concentrations (Ma et al, 2009). Similarly, Fujita et al demonstrated in rats that in contrast to sucrose gavage, oral gavage of sucralose did not induce a rise in plasma GLP-1 (Fujita et al, 2009).…”

Section: Discussionsupporting

confidence: 92%

“…This is consistent with previous human studies in which no effect on plasma glucose and insulin was observed following ingestion of encapsulated sucralose in diabetic patients (Grotz et al, 2003) or following intragastric infusion of sucralose in healthy subjects (Ma et al, 2009). Similarly, oral gavage of sucralose in rats did not improve glucose homeostasis following an intraperitoneal glucose-tolerance test (Fujita et al, 2009), suggesting that there was no incretin effect mediated by the sucralose gavage.…”

Section: Discussionsupporting

confidence: 91%

“…In support of this, recent in vitro studies failed to demonstrate an effect of sucralose on GLP-1 (Reimann et al, 2008) from enteroendocrine cells using a similar sucralose concentration to that used in this study. Furthermore, a recent in vivo study has shown that intragastric infusion of up to 40 mmol/l sucralose does not induce GLP-1 secretion in humans (Ma et al, 2009). Together with our data, these studies suggest that there is no measurable acute enhancement of GLP-1 or PYY release in vivo following oral ingestion of sucralose.…”

Section: Discussionsupporting

confidence: 81%

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Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects

et al. 2011

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Background/Objective: The sweet-taste receptor (T1r2 þ T1r3) is expressed by enteroendocrine L-cells throughout the gastrointestinal tract. Application of sucralose (a non-calorific, non-metabolisable sweetener) to L-cells in vitro stimulates glucagon-like peptide (GLP)-1 secretion, an effect that is inhibited with co-administration of a T1r2 þ T1r3 inhibitor. We conducted a randomised, single-blinded, crossover study in eight healthy subjects to investigate whether oral ingestion of sucralose could stimulate L-cell-derived GLP-1 and peptide YY (PYY) release in vivo. Methods: Fasted subjects were studied on 4 study days in random order. Subjects consumed 50 ml of either water, sucralose (0.083% w/v), a non-sweet, glucose-polymer matched for sweetness with sucralose addition (50% w/v maltodextrin þ 0.083% sucralose) or a modified sham-feeding protocol (MSF ¼ oral stimulation) of sucralose (0.083% w/v). Appetite ratings and plasma GLP-1, PYY, insulin and glucose were measured at regular time points for 120 min. At 120 min, energy intake at a buffet meal was measured. Results: Sucralose ingestion did not increase plasma GLP-1 or PYY. MSF of sucralose did not elicit a cephalic phase response for insulin or GLP-1. Maltodextrin ingestion significantly increased insulin and glucose compared with water (Po0.001). Appetite ratings and energy intake were similar for all groups. Conclusions: At this dose, oral ingestion of sucralose does not increase plasma GLP-1 or PYY concentrations and hence, does not reduce appetite in healthy subjects. Oral stimulation with sucralose had no effect on GLP-1, insulin or appetite.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 81%

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Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects

et al. 2011

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“…More recently, a mechanism involving activation of the sweet taste-receptor, gustducin, has also been proposed [33]. However, it is still unclear whether all of the above mentioned pathways are involved in mediating glucose-induced incretin hormone secretion in humans, since neither sulphonylureas nor ingestion of non-calorific non-metabolizable sweeteners have been observed to affect incretin levels in clinical studies [34][35][36]. It has been thought that glucose was able to stimulate GLP-1 secretion only via interaction with the apical (luminal) membrane of the L-cell, as intravenously infused glucose was not thought to result in elevated GLP-1 levels.…”

Section: Direct Luminal Stimulation Of Enteroendocrine Cellsmentioning

confidence: 99%

Physiology of Incretins in Health and Disease

Deacon

Åhrén²

2011

Rev Diabet Stud

112

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■ AbstractThe incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are gut peptides which are secreted by endocrine cells in the intestinal mucosa. Their plasma concentrations increase quickly following food ingestion, and carbohydrate, fat, and protein have all been shown to stimulate GLP-1 and GIP secretion. Although neural and hormonal mechanisms have also been proposed to regulate incretin hormone secretion, direct stimulation of the enteroendocrine cells by the presence of nutrients in the intestinal lumen is probably the most important factor in humans. The actions of the incretin hormones are crucial for maintaining normal islet function and glucose homeostasis. Furthermore, it is also now being recognized that incretin hormones may have other actions in addition to their glucoregulatory effects. Studies have shown that GLP-1 and GIP levels and actions may be perturbed in disease states, but interpretation of the precise relationship between disease and incretins is difficult. The balance of evidence seems to suggest that alterations in secretion and/or action of incretin hormones arise secondarily to the development of insulin resistance, glucose intolerance, and/or increases in body weight rather than being causative factors. However, these impairments may contribute to the deterioration of glycemic control in diabetic patients.

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“…However, we recently demonstrated that sucralose, in two different loads, had no effect on GLP-1, glucose-dependent insulinotrophic polypeptide or insulin secretion, and that it did not elicit any feedback response on gastric emptying in healthy human subjects (5) . While this implies that artificial sweeteners may have no therapeutic benefit in the dietary management of diabetes, other than as a substitute for carbohydrates, it remains possible that sucralose affects small intestinal carbohydrate absorption as a result of its interaction with the sweet taste receptors.…”

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confidence: 91%

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

et al. 2010

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It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0·9 % saline) or control (0·9 % saline) at 4 ml/min for 150 min (T ¼ 230 to 120 min). After 30 min (T ¼ 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2·5 %), were co-infused intraduodenally (T ¼ 0 -120 min; 4·2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagonlike peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P,0·005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.3-O-methylglucose: Sodium-dependent GLUT 1: GLUT 2: Glucagon-like peptide-1The mechanisms by which the gut senses nutrients are unclear, and the 'receptor' for detecting luminal carbohydrates has, until recently, been elusive. Recent studies indicate the presence of G-protein-coupled taste receptors, T1R2 and T1R3, and their taste signal transduction partners, the G-protein gustducin and the transient receptor potential ion channel TRPM5, in the mucosa of the mouse and human gastrointestinal tract (1,2) . These receptors, analogous to sweet taste receptors on the tongue, broadly respond to sugars and artificial sweeteners, and among several cell types, they appear to co-localise with glucagon-like peptide-1 (GLP-1)-secreting L cells (3) .It has been reported that the artificial sweetener, sucralose, stimulates the secretion of both GLP-1 and glucose-dependent insulinotrophic polypeptide from the mouse enteroendocrine cell line GLUTag (4) , and it stimulates GLP-1 secretion from the human L cell line NCI-H716 (3) , a response that is blocked by the sweet receptor antagonist, lactisole, and siRNA for a-gustducin (3) . However, we recently demonstrated that sucralose, in two different loads, had no effect on GLP-1, glucose-dependent insulinotrophic polypeptide or insulin secretion, and that it did not elicit any feedback response on gastric emptying in healthy human subjects (5) . While this implies that artificial sweeteners may have no therapeutic benefit in the dietary management of diabetes, other than as a substitute for carbohydrates, it remains possible that sucralose affects small intestinal carbohydrate absorption as a result of its interaction with the sweet taste receptors.Glucose is absorbed from the small intestine through both ...

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Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

Abstract: . Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects.

Cited by 218 publications

References 48 publications

Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects

Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects

Physiology of Incretins in Health and Disease

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects

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