Dal Jakob, Høyer Katrine Lundby, Pedersen Steen Bønløkke, Magnusson Nils Erik, Bjerring Peter, Frystyk Jan, Møller Niels, Jessen Niels, Jørgensen Jens Otto Lunde
Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
J Clin Endocrinol Metab. 2016 Oct;101(10):3716-3723. doi: 10.1210/jc.2016-1806. Epub 2016 Jul 28.
Somatostatin analogs (SAs) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling.
To compare GH and insulin signaling after iv GH exposure in acromegalic patients controlled by surgery (n = 9) or SA (n = 9).
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).
GH and insulin signalling in muscle and fat. GH and IGF-1 in serum and interstitial fluid; insulin and free fatty acids in serum.
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 (r = 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 pAKTthr 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.
用于肢端肥大症以抑制生长激素（GH）分泌和肿瘤生长的生长抑素类似物（SA）也会抑制胰岛素分泌，并可能影响GH信号传导。
比较手术控制（n = 9）或SA（n = 9）治疗的肢端肥大症患者静脉注射GH后的GH和胰岛素信号传导。
每位患者在禁食过夜后（时间t = -60至120分钟）接受3小时研究。在t = 0分钟时注射GH；在t = 0分钟、t = 30分钟（肌肉）和t = 120分钟（脂肪）时获取肌肉和脂肪活检样本。从皮肤吸引水疱中获取组织间液（t = 0分钟）。
肌肉和脂肪中的GH和胰岛素信号传导。血清和组织间液中的GH和胰岛素样生长因子-1（IGF-1）；血清中的胰岛素和游离脂肪酸。
两组在GH和IGF-1方面具有可比性。SA组的游离脂肪酸和葡萄糖水平较高；SA组脂肪中细胞因子信号传导抑制蛋白1（SOCS1）mRNA的基础水平升高，且与SA剂量呈正相关（r = 0.54；P = 0.04）。两组肌肉中均出现GH诱导的GH信号传导（磷酸化信号转导及转录激活因子5b，pSTAT5b），同时SOCS和CISH基因的表达增加。SA患者中观察到GH诱导的磷酸化苏氨酸蛋白激酶B（pAKTthr）。在两组中，GH作用后脂肪中胰岛素信号传导抑制因子磷酸酶和张力蛋白同源物（PTEN）的mRNA表达均增加。
1）GH和胰岛素信号传导特征因肢端肥大症治疗方式而异。2）SA的垂体外作用可能是其原因。3）其临床意义仍有待研究。
