Growth Hormone and Insulin Signaling in Acromegaly: Impact of Surgery Versus Somatostatin Analog Treatment

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Abstract

Context:

Somatostatin analogs (SAs) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling.

Objective:

To compare GH and insulin signaling after iv GH exposure in acromegalic patients controlled by surgery (n = 9) or SA (n = 9).

Design:

Each patient was studied for 3 hours after an overnight fast (t = −60 to 120 minutes). GH was administered at t = 0 minutes; muscle and fat biopsies were obtained at t = 0 minutes and at t = 30 minutes (muscle) and t = 120 minutes (fat). Interstitial fluid was obtained from skin suction blisters (t = 0 minutes).

Main Outcome Measures:

GH and insulin signalling in muscle and fat. GH and IGF-1 in serum and interstitial fluid; insulin and free fatty acids in serum.

Results:

The groups were comparable as regards GH and IGF-1. The SA group exhibited higher free fatty acid and glucose levels; basal suppressor of cytokine signaling protein 1 (SOCS1) mRNA in fat was increased in the SA group and correlated positively with SA dose (r2 = 0.54; P = .04). GH-induced GH signalling (pSTAT5b) in muscle occurred in both groups together with increased expression of SOCS and CISH genes. GH-induced pAKTthr308 was observed in SA patients. In both groups, mRNA expression of phosphatase and tensin homolog, a suppressor of insulin signaling, increased in fat after GH.

Conclusion:

1) Signatures of GH and insulin signaling differ as a function of acromegaly treatment modality. 2) Extra-pituitary effects of SA may account for this. 3) The clinical implications remain to be investigated.

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