Endocrine Abstracts

Attenuated glucoprivic feeding responses are a feature of hypoglycaemic unawareness in insulin-treated diabetes. Glucose alters the activity of hypothalamic neurones involved in regulating appetite. Arcuate nucleus (ARC) Neuropeptide Y (NPY) releasing neurones stimulate feeding. The identification of glucose-sensitive NPY releasing hypothalamic neurones suggests a strong role for these neurones in mediating changes in appetite induced by alterations of glucose. To gain a bette...

Leptin is an adipocyte-derived cytokine critical to the integration of energy homeostasis and reproduction which putatively acts as a metabolic gate for the onset of puberty. However, it is unknown whether the age of puberty reflects leptin levels or leptin sensitivity. If pubertal age reflects leptin sensitivity, it may also reflect susceptibility to diet-induced obesity.We hypothesised that age of pubertal onset reflects leptin sensitivity. We assessed...

Neuromedin B (NMB) is a highly conserved bombesin-related peptide found in mammals. The mammalian bombesin family of receptors consists of three closely related G protein coupled receptors, BB1, BB2 and BB3. The BB1 receptor subtype has the highest affinity for NMB. NMB mRNA is detected in the CNS and is expressed at relatively high levels in the rat hypothalamus, in particular the medial preoptic area and the arcuate nucleus.<p ...

Nesfatin is an 82 amino acid peptide identified as a novel hypothalamic regulator of feeding. In rodents, central administration of nesfatin acutely inhibits feeding and chronic administration reduces weight gain. Subsequent research has demonstrated nesfatin is involved in the control of puberty in female rats. During puberty i.c.v. administration of nesfatin stimulates release of LH and FSH but has no effect in adult female rats.We investigated the eff...

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...

The hypothalamus regulates multiple homeostatic systems, and is essential for the regulation of appetite and energy balance. Neuropeptide Y, a 36 amino acid peptide and member of the PP-fold family, is a key hypothalamic neuropeptide involved in the regulation of energy balance, potently stimulating food intake following central administration. NPY is expressed in the arcuate nucleus (ARC) and NPYergic neurones project to multiple hypothalamic nuclei and extra-hypothalamic sit...

Background and aims: Ghrelin is the only known peripheral hormone, which increases food intake. It is released from the stomach and is thought to function as a meal initiator and signal of energy deficit. We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in stomach and brain. These mice exhibited increased circulating bioactive ghrelin and as expected were hyperphagic and glucose intolerant. We hypot...

Hypoglycaemia and hypoglycaemia unawareness severely limit the optimal management of diabetes mellitus and cause recurrent morbidity and even mortality in intensively controlled patients. Altered hypothalamic glucose sensing has been implicated in the development of defective counter regulatory responses to insulin induced hypoglycaemia and hypoglycaemic unawareness. This change in hypothalamic glucose sensing has been attributed, at least in part, to an increase in glucokinas...

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...

Relaxin-3 is a newly discovered member of the insulin superfamily. It is expressed in the nucleus incertus (NI) of the brainstem which has projections to the hypothalamus. Relaxin-3 binds with high affinity to the G-protein-coupled receptors RXFP1 and RXFP3. RXFP3 is expressed predominantly in the CNS, and in particular within the hypothalamic paraventricular nucleus (PVN). The physiological function of relaxin-3 is unknown but recent work suggests it may play a role in appeti...