Endocrine Abstracts

Cholecystokinin (CCK) and secretin (SCT) are gastrointestinal hormones classically recognised for regulating pancreatic exocrine secretion and digestive processes. Their wider endocrine roles, particularly in modulating insulin secretion and glucose homeostasis, are less well understood. Incretin gut hormones (e.g. GLP-1 and GIP) can act via the circulation and also engage enteric neural circuits, which in turn communicate with peripheral organs like the pancreas. Transcriptomic data reveal that both the CCKA receptor (Cckar) and the SCT receptor (Sctr) are highly expressed in duodenal myenteric plexus neurons, raising the possibility that the enteric nervous system (ENS) may serve as a relay for gut hormone influence on endocrine function and glucose homeostasis. We therefore investigated the effects of CCK and SCT on pancreatic islets and systemic glucose regulation. Static glucose-stimulated insulin secretion (GSIS) assays were conducted in isolated mouse islets, with or without co-culture of longitudinal muscle myenteric plexus (LMMP) neurons. Intraperitoneal glucose tolerance tests (IPGTT) were also performed following hormone administration. in-vitro, neither CCK nor SCT altered insulin secretion in isolated islets. However, under neuronal co-culture, SCT significantly enhanced insulin secretion under high-glucose conditions. in vivo, the systemic effects diverged: SCT impaired glucose tolerance, increasing peak glucose, whereas CCK improved tolerance, reducing glycaemic excursions. These findings further support the notion that CCK and SCT may also play endocrine roles beyond their traditional digestive functions. The dual observation that both hormones potentiate insulin secretion in-vitro yet differentially regulate glucose tolerance in vivo highlights the complexity of gut hormone signalling. Together, these results broaden our understanding of enteroendocrine-islet interactions and suggest new perspectives on gut hormone involvement in glucose homeostasis.