Endocrine Abstracts

The preproglucagon derived peptides glucagon, glucagon-like peptide-1 (GLP-1) and oxyntomodulin are all known to inhibit appetite and have been previously shown to activate the nucleus tractus solitarius (NTS) in the brainstem. The NTS is involved in the processing of signals transmitted from the periphery to the brain via the vagus nerve. The anorectic effects of peripherally administered glucagon and GLP-1 have been shown to be diminished or ablated by subdiaphragmatic vagot...

Glucagon is released from α-cells in the pancreatic islets and is best known for its role in glucose homeostasis. Glucagon/GLP-1 receptor co-agonists have recently been shown to improve glucose homeostasis and reduce body weight in diet-induced obese mice. Glucagon receptor agonism increases energy expenditure while the GLP-1 receptor agonism prevents glucagon-induced hyperglycemia. Peripherally administered glucagon is also capable of reducing food intake, and glucagon n...

Pancreatic polypeptide (PP) is a 36 amino acid peptide, secreted from the endocrine pancreas. Previous work has shown that peripheral administration of PP inhibits food intake in rodents and humans. However, PP has a short circulating half-life that limits its use as an anti-obesity agent. Determining the mechanisms involved in the physiological breakdown of PP will allow the rational design of long-acting analogues with greater clinical utility in the treatment of obesity. PP...

Peptide YY (PYY) is a satiety hormone that communicates nutritional status to the central nervous system. PYY is released postprandially from endocrine L-cells in proportion to calories consumed. It is processed to generate the principle bioactive form PYY3–36, which acts on Y2 receptors in feeding centres within the brainstem and hypothalamus to reduce appetite. Chronic intravenous infusion of PYY3–36 induces weight loss in rodents, and obese humans display low plas...

The amelioration of type 2 diabetes and sustained weight loss after bariatric surgery are thought to be due to elevated circulating levels of the gut hormones peptide YY3–36 (PYY3–36) and glucagon-like peptide-1 (GLP-1). GLP-1 augments the insulin response to an oral glucose load. PYY3–36 has appetite-inhibitory effects and contributes to longer-term weight loss. Rodent studies provide conflicting data regarding the effects of PY...

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...

Obesity is a growing global epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs which aim to cause effective weight loss with minimal side effects. Two related peptide hormones, glucagon and glucagon-like peptide 1 (GLP-1), are the subject of this investigation. Both have been found to reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. It is...

Introduction: Peptide-YY (PYY) is produced by intestinal L-cells following nutrient ingestion. PYY analogues are an emerging class of anti-obesity medication. Peripheral administration of PYY has potent anorectic effects in rodents and humans. Interestingly, rodent studies have demonstrated that PYY has additional effects on reproductive hormone secretion depending on the model studied. In humans, hypogonadism occurs in up to 40% of men with obesity. Therefore, the effects of ...