Sweet stimuli induce cephalic phase insulin release to varying degrees in humans.

Previous work has shown that oral stimulation with glucose and glucose-containing carbohydrates induces cephalic phase insulin release (CPIR), and that inhibiting the sweet taste receptor, T1R2+T1R3, attenuates this effect in humans. It remains unclear whether perceived sweet taste in the absence of glucose is sufficient to elicit CPIR. To address this, we measured CPIR following oral exposure to glucose and two non-glucose-containing sweet stimuli, fructose and sucralose. Healthy adults (N = 28) attended three sessions where blood samples were collected before and after stimulation with one of the sweeteners. Concentrations of plasma insulin and c-peptide-a surrogate marker co-secreted with insulin in equimolar amounts-were analyzed to assess the response. While glucose and fructose stimulation elicited significant increases in c-peptide and insulin from baseline at 2 minutes (one-sample t-test, all p < 0.05), sucralose, on average, induced only a trending or non-significant increase (c-peptide, p = 0.08; insulin, p > 0.10). However, when participants' highest (peak) Δ c-peptide and Δ insulin values were considered, all three stimuli produced significant increases in both markers (all p < 0.005 for c-peptide and insulin). Furthermore, repeated measures ANOVA consistently showed no significant effect of stimulus across all metrics considered-post-stimulation Δ, highest Δ, or AUC values (all p > 0.05)-indicating the three stimuli produced comparable responses across individuals. Notably, individual-level data revealed marked variability in both time course and magnitude of CPIR across all stimuli. These findings indicate that tasting sweet stimuli can trigger CPIR in humans, but its expression varies considerably across individuals.