To elucidate the mechanism by which excessive intake of monosaccharide impairs glucose tolerance and the role of incretin

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C57BL/6J mice received a control diet (CD), a 38.5% sucrose diet (HSD) or high-starch diet (CS) for 5 weeks. An oral glucose tolerance test (OGTT) showed that plasma glucose levels in the early phase were higher in HSD group than in other groups. The OGTT also showed no differences in blood glucose levels at baseline and 60 min among three groups. Mice fed HSD showed that glucagon-like peptide-1 secretion (GLP-1) was impaired, and that insulin secretion was relatively reduced. Hepatic glucokinase activity was significantly reduced and the accumulation of glycogen in the liver was suppressed during OGTT in HSD group. We therefore demonstrate reduction in hepatic glucokinase activity and impairment in GLP-1 secretion contributes to the glucose intolerance by excessive ingestion of monosaccharide.