Non-nutritive sweeteners attenuate reinforced cephalic phase insulin release and impair glucose tolerance in mice

Non-nutritive artificial sweeteners (NNSs) which provide sweetness with minimal calories are used to reduce sugar consumption, while orosensory stimuli such as sweet taste can stimulate insulin secretion known as cephalic phase insulin release (CPIR). Whether the use of NNSs affects CPIR and glucose homeostasis remains unclear. Here, we report that NNSs impair CPIR reinforced by glucose solution conditioning and disturb glucose homeostasis in mice without affecting peripheral sensing of the tastant through the chorda tympani nerve. We established a protocol for reinforcing CPIR and detecting it in male C57BL/6 mice. Consumption of the NNSs for 2 days impaired the reinforced CPIR and the improved glucose tolerance by the consumption of 1 M glucose solution. These results suggest that NNS impairs glucose tolerance partly by disturbing CPIR in mice. • The use of non-nutritive sweetener (NNS) attenuates cephalic-phase insulin release • The use of NNSs for 2 days is sufficient to worsen glucose tolerance in mice • These changes occur without any change in the peripheral sensing of 5 basic tastes • The use of NNSs impairs glucose tolerance partly by disturbing CPIR in mice