Intestinal exposure to glucose stimulates the release of glucagon-like peptide-1 (GLP-1), slows subsequent gastric emptying, and reduces appetite. These responses are signaled, at least in part, by intestinal “sweet taste receptors” (STRs), including taste receptor type 1 members 2 and 3 (T1R2, T1R3), and their cellular signaling partners α-gustducin and transient receptor potential cation channel subfamily M member 5 (TRPM5) (1). A recent study by Brown et al. (2) in healthy humans reported that oral ingestion of “diet soda,” containing both sucralose (46 mg) and acesulfame potassium (AceK) (26 mg), augmented GLP-1 release by more than one-third after an oral glucose load given 10 min later compared with carbonated water, suggesting a potential synergy between artificial sweeteners and glucose in stimulating GLP-1 secretion. The design of that study was, however, suboptimal, as the diet soda contained a number of substances (including caramel color, gum acacia, natural flavors, citric acid, potassium benzoate, phosphoric acid, and potassium citrate) that were not controlled for. Therefore, we evaluated whether oral administration of sucralose and AceK in doses comparable with those used by Brown et al. (2) would augment the GLP-1 response to oral glucose and modulate gastric emptying or glycemia in healthy humans.
Ten healthy males (mean age 33.6 ± 5.9 years; BMI: 25.5 ± 1.0 kg/m2) were studied on four occasions each, separated by ≥3 days, in single-blinded randomized fashion. Informed consent and ethics approval were obtained. After an overnight fast, each subject consumed either 240 mL water alone or equivalently sweetened with 1) 52 mg sucralose, 2) 200 mg AceK, or 3) 46 mg sucralose plus 26 mg AceK (3). Ten minutes later, each drank 75 g of glucose, made up to 300 mL with water, and containing 150 mg 13C-acetate. Blood glucose (glucometer), plasma insulin (ELISA), total GLP-1 (radioimmunoassay), and gastric emptying (breath test) were evaluated over 240 min.
Blood glucose, plasma insulin, and total GLP-1 concentrations did not change after either water or sweetened drinks, prior to glucose ingestion, but all increased after oral glucose (P < 0.001 for each), without any difference between the 4 days (Fig. 1A–C). Neither the 13CO2:12CO2 ratio nor the half-emptying time (T50) differed between the 4 days (Fig. 1D and E).
These observations differ from those of Brown et al. (2), although the doses of sucralose and AceK and the load and timing of the subsequent glucose drink were identical in our study. It is unclear whether other components of diet soda that were not controlled for by Brown et al. may have had the capacity to stimulate GLP-1 secretion. Our findings are, however, consistent with previous reports that sucralose or AceK alone has no effect on GLP-1 secretion, insulin, or blood glucose concentrations (3,4) and our observations that sucralose had no effect on GLP-1 secretion or the glycemic response to intraduodenal glucose in healthy humans (5). That the STR antagonist, lactisole, attenuates glucose-stimulated GLP-1 secretion suggests that activation of STRs is necessary, but not sufficient, to stimulate L-cell secretion (1). In conclusion, sucralose and AceK, either alone or in combination, have no acute effect on gastric emptying, GLP-1, or glycemic responses after oral glucose in healthy humans.
This work was funded by a grant awarded by the National Health and Medical Research Council (NHMRC) of Australia (no. 627139). K.L.J.’s salary is provided by an NHMRC Senior Clinical Career Development Award (NHMRC 627011).
No potential conflicts of interest relevant to this article were reported.
T.W. was involved in study design and coordination, subject recruitment, data collection and interpretation, statistical analysis, and the drafting of the manuscript; critically reviewed the manuscript; and approved the publication of the final version of the manuscript. M.J.B. assisted with data collection, critically reviewed the manuscript, and approved the publication of the final version of the manuscript. S.D.S. performed insulin and GLP-1 assays, critically reviewed the manuscript, and approved the publication of the final version of the manuscript. M.B. performed the gastric emptying analysis, critically reviewed the manuscript, and approved the publication of the final version of the manuscript. R.L.Y., K.L.J., and M.H. were involved in the conception of the study and data interpretation, critically reviewed the manuscript, and approved the publication of the final version of the manuscript. C.K.R. was involved in conception and design of the study and data interpretation, had overall responsibility for the study, critically reviewed the manuscript, and approved the publication of the final version of the manuscript. C.K.R. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
The authors thank Kylie Lange (Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide) for her expert statistical advice.