Short-Clustered Maltodextrin Activates Ileal Glucose-Sensing and Induces Glucagon-like Peptide 1 Secretion to Ameliorate Glucose Homeostasis in Type 2 Diabetic Mice

Reconstructing molecular structure is an effective approach to attenuating glycemic response to starch. Previously, we rearranged α-1,4 and α-1,6-glycosidic bonds in starch molecules to produce short-clustered maltodextrin (SCMD). The present study revealed that SCMD slowly released glucose until the distal ileum. The activated ileal glucose-sensing enabled SCMD to be a potent inducer for glucagon-like peptide-1 (GLP-1). Furthermore, SCMD was found feasible to serve as the dominant dietary carbohydrate to rescue mice from diabetes. Interestingly, a mixture of normal maltodextrin and resistant dextrin (MD+RD), although it caused an attenuated glycemic response similar to that of SCMD, failed to ameliorate glucose homeostasis because it hardly induced GLP-1 secretion. The serum GLP-1 levels seen in MD+RD-fed mice (5.25 ± 1.51 pmol/L) were significantly lower than those seen in SCMD-fed mice (8.25 ± 2.01 pmol/L, p < 0.05). Further investigation revealed that the beneficial effects of SCMD could be abolished by a GLP-1 receptor (GLP-1R) antagonist. These results identify GLP-1R signaling as a critical contributor to SCMD-exerted health benefits and highlight the role of ileal glucose-sensing in designing dietary carbohydrates.