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

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Hammersmith Campus, Imperial College London, London, UK.
European journal of clinical nutrition (Impact Factor: 2.71). 01/2011; 65(4):508-13. DOI: 10.1038/ejcn.2010.291
Source: PubMed


The sweet-taste receptor (T1r2+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+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.
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+0.083% sucralose) or a modified sham-feeding protocol (MSF=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.
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 (P<0.001). Appetite ratings and energy intake were similar for all groups.
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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Available from: Heather E Ford, Aug 21, 2014
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    • "A series of studies conducted in human subjects have reported that sucralose does not affect the glycemic or hormonal responses to intraduodenal (15) or oral administration of glucose or other carbohydrates (16,18,33) (rev. in 13). The reason(s) for the discrepancy between findings may be related to study subject selection. "
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    ABSTRACT: OBJECTIVE Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects.RESEARCH DESIGN AND METHODS Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m(2)) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics.RESULTSCompared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose.CONCLUSIONS These data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS.
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    • "The sweet receptor, T1R2+T1R3, and its signaling pathway in L cells have been shown to regulate oral glucose-stimulated GLP-1 secretion [14]. The applications of this finding in clinical trials have not been successful to date [15] [16] [17]. There is also evidence showing that the T2R bitter taste receptors are expressed in the enteroendocrine cells in gut and cell lines [18] [19] [20]. "
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    ABSTRACT: This study aimed to examine the role of GLP-1 in the hypoglycemic activity of wild bitter gourd (Momordica charantia L., BG). In vitro, the GLP-1 secretion in STC-1, a murine enteroendocrine cell line, was dose dependently stimulated by water extract (WE), its fractions (WEL, >3 kD and WES, <3 kD), and a bitter compounds-rich fraction of BG. These stimulations were partially inhibited by probenecid, a bitter taste receptor inhibitor, and by U-73122, a phospholipase C β 2 inhibitor. These results suggested that the stimulation might involve, at least in part, certain bitter taste receptors and/or PLC β 2-signaling pathway. Two cucurbitane triterpenoids isolated from BG, 19-nor-cucurbita-5(10),6,8,22-(E),24-pentaen-3 β -ol, and 5 β ,19-epoxycucurbita-6,24-diene-3 β ,23 ξ -diol (karavilagenine E,) showed relative high efficacy in the stimulation. In vivo, mice fed BG diet showed higher insulinogenic index in an oral glucose tolerance test. A single oral dose of WE or WES pretreatment significantly improved intraperitoneal glucose tolerance. A single oral dose of WES significantly decreased glucose and increased insulin and GLP-1 in serum after 30 min. This acute hypoglycemic effect of WES was abolished by pretreatment with exendin-9, a GLP-1 receptor antagonist. Our data provide evidence that BG stimulates GLP-1 secretion which contributes, at least in part, to the antidiabetic activity of BG through an incretin effect.
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    • "A single, oral, or i.g. dose of sucralose (79, 80), aspartame (80), or acesulfame-K (80) also did not modify plasma concentrations of GLP-1 and peptide YY (peptide YY is also secreted by L-cells and reduces hunger). Furthermore, the chronic ingestion of sucralose by participants with diabetes did not affect fasting plasma levels of glucose, hemoglobin A1c (an indicator of blood glucose levels over time), and C-peptide (81). "
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    ABSTRACT: A remarkable amount of information has emerged in the past decade regarding sweet taste physiology. This article reviews these data, with a particular focus on the elucidation of the sweet taste receptor, its location and actions in taste transduction in the mouth, its nontaste functions in the gastrointestinal tract (e.g., in enteroendocrine cells), and the brain circuitry involved in the sensory processing of sweet taste. Complications in the use of rodents to model human sweet taste perception and responses are also considered. In addition, information relating to low-calorie sweeteners (LCS) is discussed in the context of these issues. Particular consideration is given to the known effects of LCS on enteroendocrine cell function.
    Full-text · Article · May 2012 · Journal of Nutrition
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