Published online May 15, 2026. doi: 10.4239/wjd.v17.i5.117132
Revised: January 20, 2026
Accepted: February 24, 2026
Published online: May 15, 2026
Processing time: 163 Days and 0.9 Hours
The loss of enteric neurons may contribute to the altered gastric emptying ob
To evaluate the impact of GES on enteric neurons in the antral myenteric plexus of diabetic beagle canines.
Adult female beagles were used to establish a diabetes mellitus (DM) (n = 6) model via intravenous injection of streptozotocin, with healthy canines as controls (n = 3). All canines were implanted with stimulation devices and received a real GES session (0.33 millisecond, 5 mA, 15 Hz, 0.2 second on, 3 seconds off) and a sham GES session (SGES) (stimulators off) of 4 weeks each in a randomized crossover design, separated by a 3-week washout period. Full-thickness antral biopsies were obtained after each session, and pancreatic biopsies were conducted at the end of the study. Hematoxylin-eosin staining was employed to measure histopathological changes in the pancreatic islets. Immunofluorescence staining of antral full-thickness sections was employed to evaluate the alterations in choline acetyltransferase (ChAT), vasoactive intestinal peptide, neuronal nitric oxide synthase (nNOS), or calretinin immunoreactive (IR) positive neurons in relation to the anti-human neuronal protein HuC/HuD. Based on different stimulations, the results were analyzed in DM + GES, DM + SGES, control + GES, and control + SGES subgroups.
Diabetic canines exhibited a significant reduction in the number and area of pancreatic islets compared with controls. The proportions of ChAT-IR and nNOS-IR neurons in the DM + SGES subgroup were significantly lower than those in the control + SGES subgroup (67.5% ± 1.8% vs 73.3% ± 1.8%, P = 0.003; 27.3% ± 1.4% vs 32.1% ± 0.7%, P = 0.001), with an upregulation of vasoactive intestinal peptide-IR neurons (51.9% ± 0.8% vs 46.8% ± 1.2%, P < 0.001). Following the 4-week GES intervention, the proportions of ChAT-IR and nNOS-IR neurons were significantly higher (73.3% ± 1.7% vs 67.5% ± 1.8%, P = 0.002; 32.1% ± 1.7% vs 27.3% ± 1.4%, P = 0.002) compared to SGES in diabetic canines. A similar increase was also observed in the proportion of nNOS-IR neurons between the GES and SGES subgroups in controls (37.5% ± 1.3% vs 32.1% ± 0.7%, P = 0.036).
Imbalanced regulation of excitatory and inhibitory neurons in the enteric nervous system occurred in streptozotocin-induced diabetic beagles, and GES improved the survival of cholinergic and nitrergic neurons in diabetic canines.
Core Tip: Experiments in small animal models have confirmed that damage to the enteric nervous system severely impairs physiological movement in the gastrointestinal system in diabetic gastroparesis. We found that the morphologic changes in gastric excitatory and inhibitory neurons are also present in streptozotocin-induced diabetic beagle canines, despite the absence of obvious manifestations of gastroparesis. High-frequency gastric electrical stimulation ameliorates the enteric nervous system in diabetic canines by upregulating choline acetyltransferase and neuronal nitric oxide synthase-immunoreactive positive neurons, these neuromodulatory effects on enteric neuronal plasticity could restore slow wave rhythms, enhance gastric emptying, and improve gastric accommodation.