EndocrinologyJan 17, 2025

Swelling of the Intestine from D-allulose in the Gut May Increase GLP-1 Hormone Release in Male Rats

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

The secretion of glucagon-like peptide-1 (GLP-1) increased with the administration of allulose, which is linked to intestinal distension.

Oral coadministration of carbonated water enhanced GLP-1 secretion when combined with allulose.
Water-soluble and poorly absorbable substances like polyethylene glycol 1000 and D-mannitol stimulated GLP-1 secretion.
Cellulose, which is insoluble, and tetra ethylene glycol, which is water-soluble and absorbable, did not promote GLP-1 secretion.
The amount of allulose administered was positively associated with GLP-1 secretion, regardless of the concentration.
The extent of GLP-1 secretion correlated with the volume and diameter of intestinal contents following allulose intake.
Intraileal administration of air also increased GLP-1 secretion, suggesting that physical stimulation plays a role.

Simplified

The secretion of glucagon-like peptide-1 (GLP-1) is promoted by various nutrients, and glucose and fructose stimulate GLP-1 secretion via intracellular metabolism. D-allulose (allulose), a nonmetabolizable epimer of D-fructose, is also effective in stimulating GLP-1 secretion, although its underlying mechanism remains unclear. We previously observed intestinal distension after the oral administration of allulose, accompanied by increased GLP-1 secretion in rats, possibly because of the low or slow absorbability of allulose. In this study, we sought to determine whether intestinal distension caused by allulose and other factors gives rise to GLP-1 secretion in rats. We found that the oral coadministration of carbonated water enhanced allulose-induced GLP-1 secretion. Polyethylene glycol 1000 and D-mannitol, which are water-soluble and poorly absorbable, stimulated GLP-1 secretion. However, cellulose (insoluble), and tetra ethylene glycol (water-soluble and absorbable) did not. The secretion of GLP-1 increased as the absolute amount of allulose increased, independent of the concentration. The extent of the GLP-1 secretory response was positively correlated with the intestinal content volume and diameter after allulose administration. Furthermore, the intraileal administration of air expanded the intestine-induced secretion of GLP-1. Our results demonstrate that allulose promotes GLP-1 secretion, at least in part, via intestinal distension as a novel GLP-1 secretory mechanism. Physical stimulation may also contribute to postprandial GLP-1 secretion.

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Swelling of the Intestine from D-allulose in the Gut May Increase GLP-1 Hormone Release in Male Rats

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