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...

High protein diets are highly satiating but hard to maintain. By understanding the mechanisms underlying these effects we may be able to identify new anti-obesity therapies. Protein is broken-down into amino acids in the gut which are detected by a series of nutrient sensors. The calcium sensing receptor (CaSR) is primarily activated by calcium ions, but is positively allosterically modulated by aromatic amino acids, especially L-phenylalanine. Sti...

High protein diets are highly satiating but hard to maintain. By understanding the mechanisms underlying these effects we may be able to identify new anti-obesity therapies. Protein is broken-down into amino acids in the gut which are detected by a series of nutrient sensors. The calcium sensing receptor (CaSR) is primarily activated by calcium ions, but is positively allosterically modulated by aromatic amino acids, especially L-phenylalanine. Sti...

Neurotensin is widely expressed in the brain and gastrointestinal tract. Centrally, neurotensin acts as a neuropeptide to suppress appetite, induce hypothermia and modulate analgesia. Peripherally, neurotensin inhibits gastric emptying and is reported to aid lipid absorption. There is also evidence that neurotensin can influence glucose homeostasis, though this role is contentious. We have found that neurotensin acutely improves insulin release and glucose tolerance in mice, a...

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...

Background: The beneficial effects of high protein diets on glucose homeostasis are thought to be in part mediated by the modulation of gastroenteropancreatic hormones by protein-derived metabolites such as amino acids. However, the precise mechanisms by which amino acids drive these beneficial effects are not well understood. Protein intake stimulates both insulin and glucagon release; glucagon is now recognized to have other metabolic roles besides increasing blood glucose l...

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...