Diabetes-Associated Neuroplastic Changes in Neuropeptide Y-Immunoreactive Enteric Neurons Along the Porcine Gastrointestinal Tract

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Diabetes mellitus is frequently associated with gastrointestinal dysfunction, in which alterations in the enteric nervous system (ENS) are considered important contributing factors. Neuropeptide Y (NPY) is a key enteric neuromodulator involved in the regulation of gastrointestinal motility, secretion, and blood flow; however, its response to diabetes remains insufficiently characterized, particularly in large animal models. This study investigated the effect of experimental diabetes on the distribution of NPY-immunoreactive enteric neurons in the porcine gastrointestinal tract. Diabetes was induced in juvenile female pigs by streptozotocin administration. Six weeks later, the stomach, duodenum, jejunum, ileum, and descending colon were collected, and the population of NPY-immunoreactive neurons in the myenteric and submucosal plexuses was evaluated by double-label immunofluorescence. Experimental diabetes significantly increased the population of NPY-immunoreactive neurons in the myenteric plexus of the stomach, jejunum, ileum, and descending colon, whereas no statistically significant changes were detected in the duodenum after correction for multiple comparisons. In the submucosal plexuses, significant increases were restricted to the inner and outer submucosal plexuses of the descending colon. These findings demonstrate that diabetes induces region- and plexus-specific neurochemical plasticity of NPY-immunoreactive enteric neurons in pigs. Given the predominantly inhibitory effects of NPY on gastrointestinal motility and secretion, together with its vasoconstrictive actions, the observed changes may contribute to altered neural regulation of gastrointestinal function during diabetes and may represent one of the mechanisms involved in diabetic gastroenteropathy.