Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2016) 41 OC13.2 | DOI: 10.1530/endoabs.41.OC13.2

ECE2016 Oral Communications Pituitary Clinical (5 abstracts)

Growth hormone and insulin signalling after acute GH exposure in patients with controlled acromegaly: impact of surgery versus somatostatin analog treatment

Jakob Dal , Katrine Lundby Høyer , Steen B Pedersen , Nils Magnusson , Peter Bjerrring , Jan Frystyk , Niels Møller , Niels Jessen & Jens Otto L Jorgensen

Aarhus University Hospital, Aarhus, Denmark.

Background: Somatostatin analogue treatment (SA) is used in acromegaly to suppress GH secretion and tumour growth. In addition, SA also suppresses insulin secretion and may impact on GH signalling in peripheral tissues.

Objective: To compare GH and insulin signalling in skeletal muscle and adipose tissue in vivo before and after a single exogenous GH bolus in patients with acromegaly controlled by either surgery alone or by ongoing treatment with a slow-release SA.

Design: Eighteen patients considered controlled by either surgery alone (n=9) or SA treatment (n=9) were studied for 3 h after an overnight fast (t=−60 min to t=120 min) with frequent blood sampling. A GH bolus was administered at t=0 min and muscle and fat biopsies were obtained at t=0 min and at t=30 min (muscle) and at t=120 min (fat). Interstitial fluid was obtained from skin suction blisters at t=0 min.

Methods: GH and IGF-I measurements in serum and interstitial fluid. Insulin and FFA levels measured in serum. Targets of GH and insulin signalling measured in muscle and fat by quantitative RT-PCR and western blotting.

Results: The two groups were comparable as regards GH and IGF-I levels. However, SA treated patients exhibited higher circulating levels of free fatty acids (P=0.04) and glucose (P=0.02). The SA treated group exhibited increased basal SOCS1 mRNA expression in adipose tissue. A distinct activation of GH signalling (STAT5 phosphorylation) in skeletal muscle was detected after GH exposure in both groups (P<0.01), which was accompanied by increased expression of SOCS and CISH genes. A significant GH-induced phosphorylation of muscle AKT was only observed in SA treated patients. In both groups the gene expression of PTEN, a negative regulator of insulin signalling, increased significantly in fat after GH exposure.

Conclusion: 1) Certain metabolic and biological signatures of GH and insulin signalling differ between acomegalic patients controlled by either surgery alone or SA treatment, 2) SA treatment unmasks an acute stimulatory effect of GH on AKT signalling in vivo, 3) These differences may be secondary to SA-induced insulin suppression of insulin.

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