Abilities of Rare Sugar Members to Release Glucagon-like Peptide-1 and Suppress Food Intake in Mice

Background/Objectives: Rare sugars, which naturally exist in small quantities, have gained attention as next-generation functional sugars due to their sweetness and low calorie content. Some of them have already been commercialized. Rare sugar-containing syrups, produced through alkaline isomerization of high-fructose corn syrup, are effective in preventing obesity and type 2 diabetes. However, the mechanisms underlying these effects remain incompletely understood. Recently, D-allulose has been found to improve hyperphagic obesity by stimulating the secretion of the intestinal hormone glucagon-like peptide-1 (GLP-1). The present study aimed to determine the comparative effects of aldohexoses (D-glucose, D-allose) and ketohexoses (D-fructose, D-allulose, D-tagatose, D-sorbose) on GLP-1 secretion and food intake in male mice. Method and Results: Single peroral administration of four ketohexoses at 1 and 3 g/kg, but not aldohexoses at 1 and 3 g/kg, significantly increased plasma GLP-1 concentrations with comparable efficacy. Moreover, these ketohexoses at 1 g/kg suppressed food intake in the short term, an effect blunted by GLP-1 receptor antagonism. In contrast, zero-calorie D-allose at 3 g/kg suppressed feeding without raising plasma GLP-1 levels. Conclusions: These results demonstrate that D-allulose, D-tagatose, and D-sorbose, which are low-calorie rare sugars classified as ketohexoses, suppress food intake through promoting GLP-1 secretion, showing their potential to prevent and/or ameliorate type 2 diabetes, obesity and related diseases.