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.
Original language | English |
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Journal | The Journal of clinical endocrinology and metabolism |
Volume | 101 |
Issue number | 10 |
Pages (from-to) | 3716-3723 |
Number of pages | 8 |
ISSN | 0021-972X |
DOIs | |
Publication status | Published - Oct 2016 |
Externally published | Yes |
Keywords
- Acromegaly/drug therapy
- Adipose Tissue/metabolism
- Female
- Human Growth Hormone/metabolism
- Humans
- Insulin/blood
- Insulin-Like Growth Factor I/metabolism
- Male
- Middle Aged
- Muscle, Skeletal/metabolism
- Outcome and Process Assessment, Health Care
- STAT5 Transcription Factor/metabolism
- Signal Transduction/drug effects
- Somatostatin/analysis