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.