Endocrine Abstracts

Neuronal glucose and insulin signals are integrated by hypothalamic neurons to regulate energy balance. These signalling mechanisms are not clearly defined in the hypothalamus, and may be altered in obesity and diabetes. This study aimed to analyse quantitatively hypothalamic expression of candidate genes in signal transduction pathways and investigate dysregulation using Zucker and Zucker Diabetic Fatty (ZDF) models.Taqman RT-PCR was used to compare exp...

Peripheral metabolic signals such as leptin, glucose and insulin are integrated by neurons in the hypothalamus to regulate both short and long term energy balance. However, the signal transduction mechanisms by which neurons sense glucose and insulin levels are unclear and specific parts of the pathways may be distinct from those in the pancreas. The aim of this study was to quantitatively analyse hypothalamic expression of genes known to be involved in pancreatic glucose/insu...

Pro-opiomelanocortin (POMC) derived peptides coordinate energy balance via central melanocortin receptors. In order to monitor central POMC expression and processing in-vivo, we have quantified the POMC derived peptides ACTH, alpha-MSH and the high molecular weight precursors POMC/proACTH in rat cerebrospinal fluid (csf). POMC/proACTH levels were significantly lower in csf samples from fasted versus fed rats (65.2 ± 4.5 pmol/l versus 112 ± 10.1 pmol/l; p = 0.00...

We have previously shown that the ACTH precursor, POMC, is present in human plasma and is the predominant secreted POMC peptide. This suggests that POMC processing is incomplete in neuroendocrine cells and regulation of the post-translational cleavage pathway is important in controlling secretion of ACTH. We have therefore analysed the dynamics of POMC processing in both AtT20 pituitary adenoma cells and primary rat pituitary cells. In both cases, large quantities of POMC, as ...

Agouti-related protein (AGRP) plays a key role in energy homeostasis with the carboxy-terminal domain acting as an endogenous antagonist of the melanocortin-4 receptor (MC4-R). It has been suggested that the amino-terminal domain of AGRP binds to syndecan-3, allowing it to regulate local concentrations of AGRP at the MC4-R. This model assumes that AGRP is secreted as a full-length peptide. However, AGRP contains several consensus prohormone convertase cleavage sites: Lys52-Lys...