Endocrine Abstracts

The screening and monitoring of intestinal diseases still provides challenges within in vivo and clinical research. For example, patients with Crohn’s disease will typically have a biannual endoscopic examination – this invasive procedure is distressing for patients and hence its frequency is limited at the expense of sufficient monitoring of pathological progression. Modalities such as CT and MRI can image the GI tract, however, they are ionising, which nor...

Obesity is a leading global health concern. The gut-brain axis is critical to appetite regulation. The vagus nerve represents the major neural pathway between the gastrointestinal tract and the central nervous system, capable of rapidly communicating information about the nutrient content from different regions of the gastrointestinal tract, directly via nutrient receptors expressed on vagal afferents and indirectly by responding to gut hormones and enteric nervous system sign...

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 enteroendoc...

Protein stimulates insulin release and improves post-prandial glycaemic excursions. The underlying mechanism has previously been attributed to gastric emptying, incretin release and direct pancreatic stimulation. However, our studies suggest the calcium sensing receptor (CaSR) in the vagus nerve plays an important role. The CaSR has a well characterised role in calcium homeostasis, but also acts as a protein metabolite sensor. In response to the amino acid products of protein ...

Growing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Gut microbial dysbiosis occurs in obesity, while high-fibre and high-protein diets, which improve glucose tolerance and induce weight loss, are associated with the generation of microbial metabolites. Understanding how the gut responds to microbial metabolites may identify mechanisms that induce satiety and improve glucoregulation, revealing novel therapeutic targets. Indole is generated f...

Neurotensin is a 13-amino acid peptide expressed in both the brain and the gastrointestinal tract where it acts as a neuropeptide and gut hormone, respectively. Centrally, neurotensin plays a role in appetite, analgesia and thermoregulation, whereas peripheral neurotensin regulates lipid absorption, gastric emptying and exocrine pancreatic secretion. The role of neurotensin in the control of glucose homeostasis currently remains unclear. We found peripheral administration of n...

High dietary protein intake can suppress appetite, drive weight loss and improve glucose homeostasis. Understanding the mechanisms by which ingested protein is sensed may reveal new therapeutic targets for metabolic disease. G-protein coupled receptor 35 (GPR35) is activated by compounds including Kynurenic acid (Kyna), a product of amino acid metabolism. GPR35 is expressed in the intestines, most highly in the colon, and has recently been identified in the afferent vagus nerv...

Neurotensin is expressed throughout the gastrointestinal tract and acts as a gut hormone. Recent work has established neurotensin modulates lipid absorption at the gastrointestinal lumen, but its role in the control of glucose homeostasis remains unclear. Neurotensin acts via three receptors, including the NtsR1 and is endogenously released following the ingestion of olive oil. Previous work in our group has identified that neurotensin acutely improves glucose tolerance in bot...

Dietary fat intake is an important source of energy and in excess can drive the development of obesity. Investigating how dietary fat intake alters neuronal activity in the brain and drives behavioural changes may help us understand the mechanisms behind high fat diet induced obesity. 2-oleoyglycerol (2-OG) is a naturally occurring unsaturated long chain fatty acid produced by fat digestion in the gut and a ligand of G protein-coupled receptor 119 (GPR119). Published data has ...

High protein diets are effective at promoting weight loss and stimulating the secretion of pancreatic hormones. Understanding the mechanisms underlying these effects may highlight new potential therapeutic targets. The calcium sensing receptor (CaSR) is stimulated by calcium and plays a critical role in calcium homeostasis. However, it is also found in many tissues unrelated to calcium regulation. CaSR activity can be modulated by aromatic amino acids, most potently by ...