The present study aimed to investigate whether
prucalopride, as a 5‑hydroxytryptamine 4 (5‑HT4) receptor agonist, improved intestinal motility by promoting the regeneration of the enteric nervous system (ENS) in rats with
diabetes mellitus (DM). A rat model of DM was established using an
intraperitoneal injection of
streptozotocin. The rats were randomly divided into four groups of 6 rats/group: Control, DM (DM model), DM + A (5 µg/kg
prucalopride) and DM + B (10 µg/kg
prucalopride). The rats in the Control group were given an equal volume of
citric acid solvent. After successful model establishment, high
blood glucose levels were maintained for 2 weeks before administration of
prucalopride. The colonic transit time was measured using the glass bead discharge method. It was revealed that the colonic transit time of diabetic rats was the longest, and this was significantly shortened in the DM + B group. Subsequently, the colons were collected. The expression levels of
Nestin,
glial fibrillary acidic protein (GFAP), SOX10, RNA‑binding
protein human
antigen D (HuD) and
ubiquitin thiolesterase (PGP9.5) were determined via immunohistochemical analysis. Immunofluorescence double staining of 5‑HT4 +
Nestin and Ki67 +
Nestin was performed. The 5‑HT level was measured using ELISA. Compared with that in the control group,
Nestin expression was significantly increased in the DM and DM + A groups, and it was concentrated in columnar epithelial cells and the mesenchyme. Furthermore, the expression levels of
Nestin in the DM + A group were higher than those in the DM group. No difference was observed in the expression levels of
Nestin between the DM + B group and the Control group. The expression levels of 5‑HT
protein were highest in the Control group; however, the expression levels of 5‑HT
protein in the DM group, DM + A group and DM + B group exhibited an increasing trend. Similar trends in the expression of 5‑HT4 and
Nestin were not observed; however, similar trends in the expression of
Nestin and Ki67 were observed. The expression levels of GFAP, SOX10, PGP9.5 and Ki67 in the DM + A and DM + B groups were higher compared with those in the DM group. In the DM + A group, HuD expression was decreased compared with that in the Control group but it was markedly higher compared with that in the DM group. In conclusion,
prucalopride may improve intestinal motility by promoting ENS regeneration in rats with DM.