Endocrine Abstracts

In light of the ever-increasing incidences of obesity and T2DM, development of novel therapeutic or preventative measures to combat these epidemics is of utmost importance. Identification of a causal relationship between an altered maternal metabolic homeostasis and an increased propensity for the unborn child to develop metabolic disorders throughout lifetime has shifted considerable amount of attention towards understanding the underlying cellular and molecular alterations. ...

Glucagon-like peptide 1 (GLP1) acts as both a peripheral incretin hormone and a central neuropeptide to regulate glucose and energy homeostasis. Within the brain, GLP1 is synthesised by a discrete collection of neurones in the brainstem, and presynaptic release of GLP1 results in binding to postsynaptic GLP1 receptors (GLP1R). The pattern of projections from these GLP1 synthesising neurones in the mouse brain has been described previously1,2. Here we use a novel tra...

Introduction: Enteroendocrine cells (EECs) are hormone-secreting cells within the intestinal epithelium that play an important role in regulating food absorption, insulin secretion and appetite. To understand the molecular mechanism governing the function of EECs, it is important to investigate cell-type-specific gene expression. The aim of this study was to identify the transcriptome of human EEC populations from organoid culture.Methods: To label the f...

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...

Autoimmune immunoglobulins directed against peptide hormones are well-described. These are often clinically benign, but may cause a deleterious effect on the accuracy of clinical immunoassays. A notable exception is Insulin Autoimmune Syndrome (IAS, also known as Hirata disease), where antibody-binding has a direct effect on insulin kinetics resulting in aberrant glucose control. Current methods to diagnose IAS rely on crude immune-subtraction techniques such as polyethylene g...

Glucagon like peptide-1 (GLP-1) is derived from selective cleavage of the preproglucagon (PPG) molecule synthesised in intestinal L-cells. The physiological action of GLP-1 is most commonly recognised as a peripherally released incretin, but a subset of neurons in the lower brainstem, the PPG neurons, also express GLP-1. The majority of PPG neuronal cell bodies are located in the nucleus of the solitary tract and their axons project to numerous sites throughout the CNS. Many o...

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...

Backgrounds and aims: Enteroendocrine cells (EECs) are hormone-secreting cells within the intestinal epithelium that play an important role in regulating food absorption, insulin secretion and appetite. The somatostatin (SST)-producing D-cell is an EEC of particular interest due to the profound inhibition exerted by SST over other EECs, highlighting D-cells as critical regulator of the enteroendocrine axis. The aim of this study was to profile the transcriptom...

The majority of the body’s 5-HT (serotonin) is produced from enterochromaffin cells (ECs) of the intestinal epithelium. 5-HT has important roles within the gastrointestinal tract in the modulation of motility, secretion and inflammation, while also signalling satiety and discomfort to the central nervous system. The factors regulating release of 5-HT from human small intestinal ECs have not been clearly elucidated: although circulating 5-HT levels typically increase after...