Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant negative disorder characterised by the occurrence of multiple adenomas including hyperplasia and/or neoplasm of the parathyroid glands, pancreatic islets and pituitary glands. Germline mutations in the menin gene predispose to the MEN1 syndrome; however, about 10–20% of patients with MEN1 do not have a detectable menin mutation. Recently, a mouse strain with a MEN1-like phenotype has been re...

Background: AMPK is a metabolic enzyme regulating the energy supply of the cell but it has antiproliferative effects as well via the up-regulation of the p53-p21 axis and inhibition of the mTOR-pathway. Somatostatin (SST) analogues reduce hormone secretion from somatotroph adenomas and tumour growth inhibition can also be achieved. SST affect several signalling pathways including the mTOR-pathway. mTOR is a mediator of a pro-proliferative pathway that can be inhibited by activ...

Background Ghrelin stimulates cell proliferation in a number of tissues including pituitary. AMPK, a heterotrimer kinase enzyme, is an important sensor and regulator of cellular energy balance. We have shown that ghrelin can change AMPK activity in various tissues and this mechanism could play a role in its metabolic effects. AMPK has recently been established to strongly inhibit cell proliferation and tumorigenesis. We therefore hypothesised that ghrelin stimulates cell proli...

Hypothalamic MC4R receptors are Galphas-coupled GPCR’s that mediate the satiety response to αMSH. MC4R expression predominates in the PVN/VMH regions of the hypothalamus, regulating satiety gene expression (e.g. Bdnf). Human MC4R mutations often result in compromised Galphas-cAMP-PKA signalling and obesity onset. However, downstream signalling pathways have yet to be elucidated. We have investigated the potential for αMSH to stimulat...

Background: Ghrelin stimulates cell proliferation in a number of tissues including pituitary. AMPK, a heterotrimer kinase enzyme, is an important sensor and regulator of cellular energy balance. We have shown that ghrelin can change AMPK activity in various tissues and this mechanism could play a role in its metabolic effects. AMPK has recently been established to strongly inhibit cell proliferation and tumorigenesis. We therefore hypothesised that ghrelin stimulates cell prol...

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gl...

Cushing’s syndrome is characterized by a diverse set of clinical manifestations, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to the metabolic syndrome. AMP-activated protein kinase (AMPK) is an intracellular energy sensor. It integrates nutritional and hormonal signals by switching on catabolic pathways, such as fatty acid oxidation and glycolysis and switching off anabolic pathways, such as fatty ...

We have recently reported that cannabinoids can stimulate hypothalamic and heart AMPK activity and can inhibit liver and adipose tissue AMPK activity in rats (Kola et al., JBC, 2005). These data are in accordance with the known orexigenic and adipogenic cannabinoid effects and also with their beneficial effects on the ischaemic heart. We have studied the effects of cannabinoids on AMPK activity in tissues from wild type (WT) and CB1 knockout (KO) mice to see if the CB1 ...

Cannabinoids and ghrelin exert hypothalamic orexigenic effects and independent peripheral effects have also been reported. We have recently reported that ghrelin and cannabinoids can stimulate hypothalamic and heart AMPK activity, and can inhibit liver and adipose tissue AMPK activity, in rats (Kola et al., JBC, 2005). These data are concordant with the known orexigenic, adipogenic and diabetogenic effects of these compounds as well as with their beneficial effects on t...

Cannabinoids and ghrelin are potent appetite stimulators. The ghrelin receptor (GHS-R1a), endocannabinoids and the cannabinoid 1 (CB1) receptor are expressed in the hypothalamus. There is evidence that the novel CB1 antagonist, rimonabant, causes weight loss by both central and peripheral effects. The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and regulates the energy metabolism within the single cell but also at whole body level. We have shown p...