Endocrine Abstracts

Introduction: The gut hormone peptide YY 3-36 (PYY3-36) is secreted postprandially from intestinal L-cells to signal satiety. Peripheral administration of PYY3-36 suppresses food intake in rodents and humans. PYY3-36-based drugs are therefore promising anti-obesity treatments. It has been proposed that circulating PYY3-36 supresses appetite via the Y2 receptor (Y2R) in the hypothalamic arcuate nucleus (ARC). The vagus nerve, the majo...

Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective treatments for type 2 diabetes and obesity. We recently described ‘biased’ peptide GLP-1R agonists modelled on exendin-4 which uncouple the pronounced endocytosis that usually accompanies GLP-1R activation, leading to prolongation of intracellular signalling responses. Here, we show that the metabolic consequences of biased GLP-1R activation in vivo are dominated by improvements in blood glucos...

As the nation gets fatter, the incidence of diabetes is also rising. The brain is now emerging as a critical mediator of blood sugar control, re-directing focus away from the traditional pancreas-centred model. The enzyme glucokinase (GK) acts as a glucose sensor in many tissues including glucose-sensitive neurones within the hypothalamic arcuate nucleus. However, the role of GK here is unclear. We investigated the role of arcuate GK in glucose homeostasis in both healthy and ...