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...

Background: Kisspeptin is a peptide product of the KiSS-1 gene and a key regulator of the hypothalamo-pituitary-gonadal axis. Pregnancy is associated with raised plasma kisspeptin concentrations. However, there is significant variation in the plasma kisspeptin levels quoted in previous studies. We investigated the effects of pre-analytical factors including processing time and anticoagulant type on plasma kisspeptin-immunoreactivity (IR) measurement.Meth...

Background: Roux-en-Y Gastric Bypass (RYGB) results in sustained weight loss. Changes in food preferences and eating behaviour are postulated as possible contributing mechanisms. Post-RYGB, patients consume less sugary and fatty food. Sweet taste detection and sensitivity have been reported to be enhanced post-surgery and this may account for changes in the palatability of food. Underlying mechanisms for the changes in sweet taste function and eating behaviour are unclear....

High protein diets suppress appetite, but are difficult to adhere to. Understanding how the gut senses protein may identify mechanisms to drive satiety. Amino acid products of protein digestion are thought to be sensed by G protein coupled receptors in the gut, including the calcium sensing receptor (CaSR). Calcium ions are the major ligand of the CaSR, but aromatic amino acids, particularly L-phenylalanine (L-Phe), allosterically modulate CaSR activity....

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...

Background: Kisspeptin is a novel hypothalamic hormone with powerful stimulatory effects on the hypothalamo-pituitary–gonadal (HPG) axis. Inactivating mutations in the kisspeptin receptor lead to pubertal failure. We have previously demonstrated that injection of kisspeptin-54 stimulates LH release in healthy men and women. Recent studies in animals suggest that endogenous kisspeptin may be involved in stimulating the GnRH pulse generator. Determining whether exogenous ad...

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Clinical Endocrinology 2016 84 939–945. DOI: 10.1111/cen.12603...

Background: Hypothalamic KNDy neurons have recently been identified as key regulators of reproductive function by releasing three neuropeptides namely kisspeptin, neurokinin B (NKB) and dynorphin. Animal studies show they interact to control pulsatile GnRH release, which is vital for fertility. In animals, kisspeptin stimulates, NKB modulates and the opioid dynorphin inhibits GnRH pulsatility. However, the interaction of these peptides has never been studied in humans. To inve...

The physiological post-prandial release of the gut hormones PYY and GLP-1 is implicated in triggering CNS mechanisms underlying satiety. However, the combined effects of PYY and GLP-1 on brain circuits underlying satiety in humans remain unknown.Objective: To determine changes in CNS neuronal activity following single and combined infusions of PYY and GLP-1, using blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) in human vol...