Endocrine Abstracts

The regulation of insulin and glucagon secretion has traditionally been attributed to the gut-brain axis and direct sensing of blood glucose levels by pancreatic islets. However, the enteric nervous system may directly modulate pancreatic hormone release. This study focuses on a specific population of enteric neurons that exhibit the capability to transmit signals from the gut to the pancreas, potentially revealing new pathways of metabolic regulation. The gastrointestinal tract senses various nutrients, triggering the release of hormones and neuropeptides. This research aimed to investigate the impact of enteric neuronal signalling on pancreatic hormone regulation, particularly in response to nutrient intake. In this investigation, we found that both whey and olive oil decreased blood glucose levels and improved glucose tolerance. Subsequently, we performed a surgical procedure to physically separate the proximal duodenum from the adjacent pancreas, severing the enteric neurons that project directly to the pancreas. This resulted in the attenuation of the observed effect of olive oil on glucose tolerance. Further confirmation is needed to determine the effect of whey protein in this context. To examine the specific enteric neuronal projections to the pancreas, we isolated and cultured the longitudinal muscle myenteric plexus (LMMP) of the enteric nerve. This isolation allowed us to investigate the effects of specific nutrients on the LMMP, potentially uncovering their role in pancreatic hormone regulation. Additionally, following injection of an adeno-associated virus encoding a fluorescent marker into the pancreas, we were able to identify enteric neurons with projections to the pancreas in the duodenal LMMP, and to isolate these cells and characterize their gene expression using Fluorescence-Activated Cell Sorting. This isolation will enable us to comprehensively characterize these neurons and identify their likely functions. These findings will contribute to a better understanding of pancreatic hormone regulation and offer potential therapeutic targets for metabolic disorders.