Glucagon-like peptide 1 receptor (GLP-1R) expression by nerve fibres in inflammatory bowel disease and functional effects in cultured neurons.

Introduction: Glucagon like-peptide 1 receptor (GLP-1R) agonists diminish appetite and may contribute to the weight loss in inflammatory bowel disease (IBD).

Objectives: The aim of this study was to determine, for the first time, the expression of GLP-1R by colon nerve fibres in patients with IBD, and functional effects of its agonists in cultured rat and human sensory neurons.

Methods: GLP-1R and other nerve markers were studied by immunohistochemistry in colon biopsies from patients with IBD (n = 16) and controls (n = 8), human dorsal root ganglia (DRG) tissue, and in GLP-1R transfected HEK293 cells.

Development of a UHPLC-MS/MS (SRM) method for the quantitation of endogenous glucagon and dosed GLP-1 from human plasma.

Aim: The performance of glucagon and GLP-1 immunoassays is often poor, but few sensitive LC-MS/MS methods exist as alternatives.

Experimental: A multiplexed LC-MS/MS method using a 2D extraction technique was developed.

Results: The method was established for the quantitation of endogenous glucagon (LLOQ: 15 pg/ml) and dosed GLP-1 (LLOQ: 25 pg/ml) in human plasma, and is the first such method avoiding immunoenrichment.

Impact of Duodenal-Jejunal Exclusion on Satiety Hormones.

Objective: Bariatric procedures that exclude the proximal small intestine lead to significant weight loss which is probably mediated by changes in hormones that alter appetite, such as peptide YY (PYY), ghrelin, cholecystokinin (CCK), and leptin. Here, the effect of the non-surgical duodenal-jejunal bypass liner (DJBL) on concentrations of hormones implicated in appetite control was investigated.

Subjects: A two-center prospective study was conducted between January and December 2010.

Glucokinase activity in the arcuate nucleus regulates glucose intake.

The brain relies on a constant supply of glucose, its primary fuel, for optimal function. A taste-independent mechanism within the CNS that promotes glucose delivery to the brain has been postulated to maintain glucose homeostasis; however, evidence for such a mechanism is lacking. Here, we determined that glucokinase activity within the hypothalamic arcuate nucleus is involved in regulation of dietary glucose intake.

The future role of gut hormones in the treatment of obesity.

The obesity pandemic presents a significant burden, both in terms of healthcare and economic outcomes, and current medical therapies are inadequate to deal with this challenge. Bariatric surgery is currently the only therapy available for obesity which results in long-term, sustained weight loss. The favourable effects of this surgery are thought, at least in part, to be mediated via the changes of gut hormones such as GLP-1, PYY, PP and oxyntomodulin seen following the procedure.

Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol.

Elesclomol is a novel anticancer agent that has been evaluated in a number of late stage clinical trials. A new and convenient synthesis of elesclomol and its copper complex is described. X-ray crystallographic characterization and the electrochemical properties of the elesclomol copper(II) complex are discussed.

Measurement of gut hormones in plasma.

The gastrointestinal tract is the largest endocrine organ and was the site where the first hormones were discovered: secretin in 1902 and gastrin in 1905. Discovery of these gut peptides led to the concept of blood-borne communication between cells. Gut peptide hormones and neurotransmitters regulate the complex processes of digestion, motility, epithelial growth, and integrity.

Endoscopic duodenal-jejunal bypass liner rapidly improves type 2 diabetes.

Background: Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal-jejunal bypass liner (DJBL).

Methods: Seventeen obese patients (BMI 30-50 kg/m(2)) with type 2 diabetes received the DJBL for 24 weeks.

Increased energy expenditure in gastric bypass rats is not caused by activated brown adipose tissue.

Objective: To investigate whether gastric bypass induces a higher activity of brown adipose tissue and greater levels of the brown adipose tissue-specific protein uncoupling protein-1 (UCP-1) in rats.

Methods: Gastric bypass rats and sham-operated controls (each n = 8) underwent whole body (1)H-MR spectroscopy for analysis of body composition and (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography ((18)F-FDG PET/CT) imaging for measurement of the metabolic activity of brown adipose tissue. Brown adipose tissue was harvested and weighed, and UCP-1 mRNA content was measured by Northern Blot technique.

The gut hormone response following Roux-en-Y gastric bypass: cross-sectional and prospective study.

Background: Bariatric surgery is the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass. Although there is increasing interest in the gut hormone changes after gastric bypass, the long-term changes have not been fully elucidated.

Methods: Thirty-four participants were studied cross-sectionally at four different time points, pre-operatively (n = 17) and 12 (n = 6), 18 (n = 5) and 24 months (n = 6) after laparoscopic Roux-en-Y gastric bypass.

Role of gut hormones in obesity.

A critical role for the gut in energy homeostasis has emerged. Gut hormones not only have a role in digestion but several of them have been found to modulate appetite in animals and humans. Current nonendocrine drugs for obesity are limited by their modest efficacies, and bariatric surgery is confined to use in severe cases.

Hypothalamic regulation of appetite.

The prevalence of obesity is steadily rising and has huge health and financial implications for society. Weight gain is due to an imbalance between dietary intake and energy expenditure and research has focused on trying to understand the complex pathways involved in controlling these aspects. This review highlights the key areas of research in the hypothalamic control of appetite.

Ghrelin gets its GOAT.

Ghrelin, a powerful appetite-stimulating hormone secreted by the stomach, is modified by an octanyl side chain on its third amino acid, a serine, which is essential for its activity. A recent study (Yang et al., 2008) reports identification of the enzyme catalyzing the addition of this octanyl, GOAT.

The obesity pipeline: current strategies in the development of anti-obesity drugs.

This review provides a summary of currently available pharmaceutical therapies for the treatment of obesity, along with an overview of the pipeline of products currently in development, and the key mechanisms on which the major development candidates are based. In particular, the recent increase in understanding of the role of gut peptides in energy homeostasis is highlighted as a promising source of potential future obesity therapies.

Peptide YY (PYY) is increased in elderly patients with femoral neck fractures: a prospective cohort study.

Background: Peptide YY (PYY), a gut peptide, has recently been shown to inhibit appetite. The role of this peptide in elderly nutritionally-compromised patients with femoral neck fracture (FNF) has not been investigated. In this study, we investigated the longitudinal pattern of PYY levels during hospital stay and investigated the postprandial PYY response to a standard meal in patients with FNF and matched controls.

Endocrinology: the next 60 years.

The next 60 years promise to arouse the interest of scientists and clinicians while challenging the central dogmas of endocrine physiology. In this review we consider the fundamental changes in the understanding of endocrine physiology that have taken place in recent years and the new hormones discovered. We discuss how the brain is emerging as an important regulator of endocrine and neuroendocrine circuits.

Gastrointestinal hormones regulating appetite.

The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut.

Measurement of gut hormones in plasma.

The gastrointestinal tract is the largest endocrine organ and holds a special place in endocrinology since the concept of blood-borne communication between cells was first established through experiments on the gut. Gut peptide hormones and neurotransmitters regulate the complex processes of digestion, motility, epithelial growth, and integrity. Investigation of this complex endocrine organ has depended on the development of sensitive and specific radioimmunoassay.

Gut feeling--the secret of satiety?

The worsening global epidemic of obesity has increased the urgency of research aimed at understanding the mechanisms of appetite regulation. An important aspect of the complex pathways involved in modulating energy intake is the interaction between hormonal signals of energy status released from the gut in response to a meal, and appetite centres in the brain and brainstem. In particular, the gut peptides cholecystokinin, peptide YY, glucagon-like peptide 1, oxyntomodulin and pancreatic polypeptide have been implicated in signaling satiety post-prandially.

Appetite control.

Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits.

The gut and regulation of body weight.

Signals generated by the gastrointestinal tract are able to regulate appetite and influence body weight. Ghrelin is an orexigenic peptide produced by the stomach. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin.

Gastrointestinal satiety signals III. Glucagon-like peptide 1, oxyntomodulin, peptide YY, and pancreatic polypeptide.

Many peptides are synthesized and released from the gastrointestinal tract and pancreas, including pancreatic polypeptide (PP) and the products of the gastrointestinal L cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY). Whereas their roles in regulation of gastrointestinal function have been known for some time, it is now evident that they also influence eating behavior. This review considers the anorectic peptides PYY, PP, GLP-1, and oxyntomodulin, which decrease appetite and promote satiety in both animal models and humans.