Endocrine Abstracts

Retrograde tracing studies in rodents have revealed that neurons in the myenteric plexus of the stomach’s antrum and in the initial segment of the duodenum extend to the pancreas (1). Through viral tracing, our preliminary data has shown that neurons in the myenteric plexus in the upper duodenum project directly to the pancreas. Furthermore, physical separation of the duodenum from the pancreas abolished the improvement in glucose tolerance observed in mice treated with olive oil (2). However, whether the neurons originating in the antrum of stomach also innervate the endocrine pancreas, and their specific functional role remains unknown. To investigate whether neurons from the gastric antrum also project to the pancreas, pAAV-hSyn-EGFP was injected into pancreas and confirmed EGFP expression in the stomach. Surgical separation of the pancreas from the pyloric region of the stomach was performed and verified histologically. The separation did not affect fasting blood glucose levels or body weight. Separation surgery resulted in a more rapid decline in blood glucose following an oral glucose tolerance test compared with sham-operated controls. No significant effect was observed in intraperitoneal glucose tolrance suggesting a gastrointestinal tract specific mechanism. Gastric distension induced by oral gavage of methyl cellulose or fast-refeed had no significant impact on glucose tolerance. These findings suggest that neurons connecting the stomach and pancreas may normally suppress oral glucose tolerance, and that disrupting this communication enhances the glycaemic response to ingested glucose. This effect appears to be independent of mechanical gastric signals and may represent a novel target for metabolic disease intervention.

References: 1. Kirchgessner AL, Gershon MD. Innervation of the pancreas by neurons in the gut. J Neurosci. 1990;10(5):1626–42. 2. Roberts AG, Meyer L, Norton M, et al. Enteropancreatic neurons drive the glucoregulatory response to ingested lipid. bioRxiv. 2025. https://doi.org/10.1101/2025.05.09.652620