Niels Jessen

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

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CONTEXT: Somatostatin analogues (SA) 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 intravenous GH exposure in acromegalic patients controlled by surgery (n=9) or SA (n=9).

DESIGN: Each patient was studied for 3 h after an overnight fast (t= -60 min to t = 120 min). GH was administered at t = 0 min, muscle and fat biopsies obtained at t = 0 min and t = 30 min (muscle) and t = 120 min (fat). Interstitial fluid was obtained from skin suction blisters (t = 0 min).

MAIN OUTCOME MEASURES: GH and insulin signalling in muscle and fat. GH and IGF-I in serum and interstitial fluid; insulin and FFA in serum.

RESULTS: The groups were comparable as regards GH and IGF-I. The SA group exhibited higher FFA and glucose levels; basal SOCS1 mRNA in fat was increased in the SA group and correlated positively with SA dose (r(2)= 0.54, P=0.04). GH-induced GH signalling (pSTAT5b) in muscle occurred in both groups together with increased expression of SOCS and CISH genes. GH-induced pAKTthr(308) was observed in SA patients. In both groups mRNA expression of PTEN, a suppressor of insulin signalling, 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.

OriginalsprogEngelsk
TidsskriftEndocrinology
Vol/bind101
Nummer10
Sider (fra-til)3716-3723
Antal sider8
ISSN0013-7227
DOI
StatusUdgivet - okt. 2016

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