Metabolic Effects of Non-Nutritive Sweeteners

Background Consumption of non-nutritive sweeteners is common practice in the US, and these chemicals are generally thought to be metabolically inert. However, recent data obtained from animal studies demonstrate that non-nutritive sweeteners play an active metabolic role within the gastrointestinal tract. Sweet-taste receptors, including the T1R family and Alpha-gustducin, respond not only to caloric sugars such as sucrose, but also to non-nutritive sweeteners, including sucralose (Splenda ) and acesulfame-K . In both humans and animals, these receptors have been shown to be present in glucagon-like-peptide-1 (GLP-1) secreting L cells of the gut mucosa as well as in lingual taste buds , and serve as critical mediators of GLP-1 secretion . We have demonstrated in a previous study that diet soda augments glucose-stimulated GLP-1 secretion . In addition, there is evidence in animals that activation of intestinal sweet-taste receptors by non-nutritive sweeteners enhances intestinal glucose absorption via upregulation of the glucose transporter, GLUT2 . Aims The purpose of this study is to broadly explore the effects of non-nutritive sweeteners on glucose and glucoregulatory hormones in healthy humans. To this end, we plan the following: Primary Aim: To confirm that the non-nutritive sweetener sucralose (versus other ingredients in diet soda) augments glucose-stimulated GLP-1 secretion Secondary Aims: 1. To study whether increased GLP-1 secretion due to non-nutritive sweeteners alters gastric emptying or satiety 2. To determine a dose-response relationship for non-nutritive sweeteners on glucose-stimulated GLP-1 secretion 3. To determine whether non-nutritive sweeteners alter the rate of intestinal glucose absorption 4. To test whether non-nutritive sweeteners affect levels of other incretin or gut hormones Methods Healthy men and women ages greater than or equal to 18 years, and prepubertal children ages 6-12 years, across a wide range of body mass indices will participate in a variety of paired experiments, in randomized order, with each subject serving as his or her own control. In each experiment, the subject will ingest either a non-nutritive sweetener or control, and a glucose load (oral glucose tolerance test). The following measurements will be obtained: 1. Serial measurement of glucose, insulin, C-peptide, GLP-1, and other incretin and gut hormones 2. Rate of gastric emptying using acetaminophen labeling in the oral glucose or mixed meal 3. Measurement of hunger and satiety using validated questionnaires 4. Measurement of intestinal glucose absorption using a glucose analog