Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 P179

SFEBES2008 Poster Presentations Endocrine tumours and neoplasia (31 abstracts)

Somatostatin analogues stimulate AMPK (AMP-dependent protein kinase), a metabolic enzyme with anti-proliferative effects

Chrysanthia A Leontiou 1 , Herbert Schmid 2 , Paul McSheehy 2 , Ashley B Grossman 1 & Márta Korbonits 1


1Department of Endocrinology, Barts and the London Medical School, William Harvey Research Institute, London, UK; 2Novartis Pharma AG, Basel, Switzerland.


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 activation of the enzyme AMPK, a sensor of fuel availability. We hypothesised that SST stimulates AMPK and this could contribute to its anti-proliferative effect.

Methods: The effect of octreotide and SOM230 was studied in intact rats (30 μg/kg) and in rats implanted (10 μg/kg per hour) with the rat somatomammotroph tumour cell line, GH3, on tissue (pituitary, hypothalamus, pancreas, heart, liver and adipose tissue) AMPK activity. We examined AMPK activity by using a functional kinase assay using γ32P-ATP.

Results: Octreotide significantly increased AMPK activity in implanted GH3 tumours (224±24% of control) and in the pituitary of these animals (158±11% of control). In the intact rats both octreotide and SOM230 significantly increased AMPK activity in the pituitary (147±12 and 138±9% of control, respectively). In the hypothalamus and the pancreas only octreotide had a significant effect on AMPK activity (254±53 and 186±7% of control, respectively) and in the heart only the effect of SOM230 attained significance (328±43% of control). No effect was observed in the liver.

Conclusion: We propose that the anti-proliferative effects of SST involve the stimulation of AMPK, which via the p53-p21 and Akt-mTOR-S6kinase pathways can influence tumour control.

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