Novel factors underlying novel gut-brain-pancreas cross talk

Theme: Bioscience for Health

Gut hormones underlie the coordination of post-prandial nutrient disposition and appetite. They are released from enteroendocrine cells (EECs) located in the intestinal epithelium and are differentially secreted in states of fasting and refeeding. They convey alimentation-related signals from the gut to the brain and pancreas. Gut hormones have a proven track record as therapeutic agents, led by the glucagon-like peptide-1 (GLP-1) mimetics that underpin a multi-billion pound global market for the treatment of type 2 diabetes, and have been recently approved as anti-obesity agents . Further gut hormone-based approaches are under development in the metabolism/obesity arena.

This project will exploit the idea that the gut produces a wider repertoire of hormones than hitherto identified, and that factors secreted by the gut underlie the resolution of type 2 diabetes observed in the majority of people undergoing gastric bypass surgery. The project involves transcriptomic- and mass-spectrometry (MS)-based approaches to identify novel peptides secreted from the gastrointestinal tract, exploring their physiology in rodent models and to determine how circulating gut peptide concentrations change in humans with obesity and bypass surgery.