Low-calorie sweeteners cause only limited metabolic effects in mice.

There are widespread concerns that low-calorie sweeteners (LCSs) cause metabolic derangement. These concerns stem in part from prior studies linking LCS consumption to impaired glucose tolerance in humans and rodents. Here, we examined this linkage in mice. In experiment 1, we provided mice with chow, water, and an LCS-sweetened solution (saccharin, sucralose, or acesulfame K) for 28 days and measured glucose tolerance and body weight across the exposure period. Exposure to the LCS solutions did not impair glucose tolerance or alter weight gain. In experiment 2, we provided mice with chow, water, and a solution containing saccharin, glucose, or a mixture of both for 28 days, and tested for metabolic changes. Exposure to the saccharin solution increased the insulinemic response of mice to the glucose challenge, and exposure to the saccharin + glucose solution increased the rate of glucose uptake during the glucose challenge. However, neither of these test solutions altered glucose tolerance, insulin sensitivity, plasma triglycerides, or percent body fat. In contrast, exposure to the glucose solution increased glucose tolerance, early insulin response, insulin sensitivity, and percent body fat. We conclude that whereas the LCS-containing solutions induced a few metabolic changes, they were modest compared with those induced by the glucose solution.

Taste of glucose elicits cephalic-phase insulin release in mice.

We reported previously that when C57BL/6 (B6) mice ingest glucose, plasma insulin levels rise above baseline before blood glucose levels do so. This observation led us to speculate that the taste of glucose elicits cephalic-phase insulin release (CPIR) in mice. Here, we examined the specific contributions of taste and glucose to CPIR. In Experiment 1, we bypassed the mouth and delivered glucose directly to the stomach. We found that plasma insulin levels did not rise above baseline until after blood glucose levels did so. This revealed that taste stimulation is necessary for rapid insulin release (i.e., CPIR) in mice. In Experiment 2, we examined the observation that sucrose, maltose and Polycose (a maltodextrin) all elicit CPIR. We proposed in a prior study that these carbohydrates did not directly elicit CPIR; instead, they were digested by oral amylases and alpha-glucosidases, and that it was the enzymatically liberated glucose that elicited CPIR. In support of this possibility, we reported that acarbose (an alpha-glucosidase inhibitor) prevented sucrose, maltose and Polycose from eliciting CPIR. Here, we sought to confirm that glucose alone could elicit CPIR in the presence of acarbose. Indeed, we found that glucose alone and glucose+acarbose each elicited equally robust CPIR. Taken together, these results provide further support for the hypothesis that mice possess a glucose-specific taste transduction pathway that triggers rapid insulin release.