ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P177 | DOI: 10.1530/endoabs.65.P177

Investigating the role of GPR119 in the vagus nerve

Sijing Cheng, Anna Roberts, Mariana Norton, Bryn Owen, Aylin Hanyaloglu & Kevin Murphy

Imperial College Londo, London, UK

The prevalence of obesity and its associated metabolic diseases are increasing, but current treatments are ineffective or impractical. Understanding how the gut–brain axis senses nutrients to regulate appetite and glucose homeostasis may identify new drug targets and treatments. The G protein-coupled receptor 119 (GPR119) has several endogenous lipid ligands and has been proposed to act as a nutrient sensor in the gastrointestinal tract. GPR119 is expressed on enteroendocrine cells and pancreas, and has been shown to have beneficial effects on glucose homeostasis, at least in part because it can stimulate the release of incretins. It has also been found to suppress food intake, making GPR119 a potential target for type 2 diabetes treatments, though to date synthetic ligands have proved largely ineffective. Understanding how GPR119 can regulate energy and glucose homeostasis may facilitate better drug design and targeting. The vagus nerve permits neuronal signalling between the gastrointestinal tract and brainstem, and playing an important role in appetite regulation. GPR119 has recently been found to be expressed in the nodose ganglia (NG), where the cell bodies of vagal afferent neurons reside. Our data show that murine GPR119 is highly expressed in both the left and right NG compared to gastrointestinal tract tissues (duodenum, jejunum, ileum, and colon). However, fasting did not significantly alter GPR119 expression in any tissues examined. In vitro cultured murine NG cells were treated with the endogenous GPR119 ligand, oleoylethanolamide (OEA, 10 mM) or the synthetic GPR119 ligand, AR231453 (400 nM). Both agonists increased intracellular calcium mobilization in NG cells. However, oral gavage of 30 mg/kg OEA did not alter the response to a glucose tolerance test or influence food intake in mice. Further work is required to determine whether other GPR119 ligands may influence metabolic regulation through the vagus nerve, and whether these systems represent useful therapeutic targets.

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