Roberts, A. G.; Meyer, L.; Norton, M.; Phuah, P.; Martin Alonso, A.; Dowsett, G. K.; Cheng, S.; Dunsterville, C.; Liu, J.; Chung, P.-E.; Tao, Y.; Smitherman-Cairns, T.; Deutsch, A. B.; Chatterjee, A.; Lam, B. Y.; Hanyaloglu, A.; Jones, B.; Yeo, G. S. H.; Salem, V.; Murphy, K. G.

Enteropancreatic neurons project from the small intestinal wall to the pancreas. Though well positioned to mediate the effects of ingested nutrients on pancreatic function, the metabolic role of these neurons is unclear. Diets rich in olive oil promote weight loss and improve remission rates in patients with T2DM. Here, we show that olive oil improves acute glucose tolerance by stimulating insulin release via neurotensin receptor type 1 (NTSR1)-expressing enteropancreatic neurons. These neurons are necessary for the effects of olive and neurotensin on glucose tolerance, and their activation is sufficient to improve glucose tolerance. These findings suggest a mechanism by which dietary olive oil regulates blood glucose levels and present a novel functional role for enteropancreatic neurons in regulating glucose homeostasis.