Searchable abstracts of presentations at key conferences in endocrinology

ea0019p123 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Expression of ghrelin O-acyltransferase (GOAT), the newly-identified ghrelin acylation enzyme, in various human tissues

Lim CT , Kola B , Igreja S , Grossman AB , Korbonits M

Ghrelin is a circulating growth hormone-releasing and appetite-inducing brain–gut peptide. It needs to be acylated on its serine-3 with octanoate for its endocrine actions. The acyl-transferase that catalyses ghrelin octanoylation has been recently identified and named GOAT (ghrelin O-acyltransferase), which is coded by the MBOAT4 gene. This study aimed to investigate GOAT expression in human. The distribution of GOAT mRNA expression was studied in various human ti...

ea0019oc22 | Cardiovascular metabolism | SFEBES2009

The effects of ghrelin and cannabinoids on AMP-activated protein kinase (AMPK) activity in growth hormone-secretagogue receptor (GHS-R) knockout mice

Lim CT , Kola B , Feltrin D , Perez-Tilve D , Grossman AB , Tschop MH , Korbonits M

Introduction: Ghrelin is a potent orexigenic brain-gut peptide with lipogenic and diabetogenic effects, possibly mediated by GHS-R. Cannabinoids also have orexigenic and lipogenic effects. AMPK is a regulator of energy homeostasis and we have previously shown that ghrelin and cannabinoids stimulate hypothalamic AMPK activity while inhibiting it in liver and adipose tissue, suggesting that AMPK mediates both the central appetite-inducing and peripheral effects of ghrelin and ca...

ea0012p121 | Steroids to include Cushing's | SFE2006

Role of glucocorticoids and AMPK in the regulation of lipogenesis and glycerogenesis in mesenteric adipose tissue

Lolli F , Christ-Crain M , Kola B , Wittman G , Fekete C , Grossman AB , Korbonits M

CushingÂ’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 ...

ea0011oc25 | Diabetes and metabolism | ECE2006

Cannabinoids increase AMP-activated protein kinase (AMPK) enzyme activity in the hypothalamus and heart via different signalling pathways – studies in CB1 knockout animals

Kola B , Christ-Crain M , Wittman G , Leontiou C , Grossman A , Fekete C , Korbonits M

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 ...

ea0011p383 | Diabetes, metabolism and cardiovascular | ECE2006

Direct effect of cannabinoids and ghrelin on liver and adipose cell metabolism via the AMP-activated protein kinase (AMPK) enzyme

Dalino P , Aguilar D , Isidori AM , Hubina E , Garcia EA , Kola B , Grossman AB , Korbonits M

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...

ea0010oc6 | Reproduction, neuroendocrinology and diabetes | SFE2005

Ghrelin and cannabinoids increase food intake via stimulation of hypothalamic amp-activated protein kinase (AMPK)

Adams V , Kola B , Garcia E , Hubina E , Dalino P , Khalaf S , Grossman|M##Korbonits A

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...

ea0007p82 | Endocrine tumours and neoplasia | BES2004

Over-expression and over-activation of protein kinase B/Akt in human pituitary tumours

Musat M , Korbonits M , Kola B , Nanzer A , Morris D , Coculescu M , Grossman A

Mitogenic signaling by receptor tyrosine kinases that involve increased activity of phosphatidylinositol-3-kinase (PI3K) and over-activation of protein kinase B (PKB/Akt) triggers a cascade of responses that drive tumour progression in a variety of human cancers. Some of these events have been associated with diminished expression of the cell cycle inhibitor p27 through inhibition of a Forkhead transcription factor (FKHR-L1) by Akt, while some others have recently been reporte...

ea0003p140 | Endocrine Tumours and Neoplasia | BES2002

Growth hormone receptor and type 1 IGF receptor in human somatotroph tumours

Kola B , Korbonits M , Powell M , Metherell L , Czirjak S , Boscaro M , Mantero F , Grossman A

Aim: Clinical acromegaly is characterized by high GH secretion in the presence of high circulating IGF-I levels. We therefore hypothesized that the physiological IGF-I-GH negative feedback loop may be reset in somatotroph adenomas, and we investigated the role of type 1 IGF receptor (IGF-R) and GH receptor (GHR) by quantifying mRNA expression in somatotroph tumours, and investigated the possible presence of mutations of the GHR gene.Methods: Pituitary t...

ea0008oc19 | Young Endocrinologist Session | SFE2004

Proliferative effects of ghrelin and desoctanoyl ghrelin are independent of the growth hormone secretagogue receptor (GHS-R)

Marsh VB , Kola B , Hanson M , Emery M , Musat M , Bonner S , Khalaf S , Norman D , Grossman A , Korbonits M

Background: Ghrelin was recently discovered as the natural ligand for the G protein-coupled growth hormone secretagogue receptor and induces GH release through GHS-R1a. The octanoylation of its third serine residue is responsible for GH release and receptor binding. A variant of ghrelin devoid of this modification, desoctanoyl-ghrelin, can neither bind to the receptor nor induce GH release. Ghrelin has also been shown to effect cellular proliferation, being pro-proliferative i...

ea0005p130 | Endocrine Tumours and Neoplasia | BES2003

Identification of the ACTH receptor in the human pituitary and its loss of expression in pituitary adenomas

Morris D , Kola B , Borboli N , Kaltsas G , Gueorguiev M , Jones T , Baldeweg S , Powell M , Korbonits M , Grossman A

The ACTH receptor (ACTH-R) is the second member of the melanocortin receptor family that includes five seven-transmembrane G protein-coupled receptors, and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short loop feedback within the pituitary, and as ACTH-secreting adenomas are characterised by resistance to glucocorticoid feedback, they may also have dysregulated ACTH feedback....