Department of Internal Medicine and Endocrinology (MEA), Aarhus University Hospital, Aarhus C, Denmark.
J Clin Endocrinol Metab. 2011 Aug;96(8):2581-9. doi: 10.1210/jc.2011-0592. Epub 2011 Jun 1.
Evidence suggests that somatostatin not only inhibits the secretion of GH but also suppresses GH action in peripheral tissues.
We tested the hypothesis that somatostatin suppresses GH activity in human skeletal muscle in vivo.
Eight healthy young men (25.3 ± 2.8 yr) were studied on a single occasion after an overnight fast for 4 h [including a basal period (0-2 h) and a hyperinsulinemic euglycemic clamp (2-4 h)] during an iv GH infusion (50 ng/kg⁻¹ · min⁻¹). Each subject received an intraarterial somatostatin infusion (150 μg/h⁻¹) into one femoral artery and an intraarterial saline infusion into the contra lateral artery. The simultaneous blood samples were drawn from both femoral veins. Muscle biopsies were obtained from one leg at t = 0 and from both legs during the basal period and during the clamp.
Muscle glucose uptake, signaling proteins for GH (phosphorylated signal transducer and activator of transcription-5) and insulin (phosphorylation of AS160), and expression of GH-regulated genes (IGF-I and suppressor of cytokine signaling 1-3) were measured.
Somatostatin significantly increased glucose uptake measured by arteriovenous glucose difference during the basal period (P = 0.03) but not during the clamp. There was a tendency for the phosphorylation of AS160 to be higher in the somatostatin-infused leg compared with the saline leg (P = 0.055). The expression of suppressor of cytokine signaling-1 mRNA was significantly elevated in the clamp-biopsy from the saline-infused leg (P = 0.024).
We concluded the following: 1) in the presence of systemic GH exposure, somatostatin increases basal glucose uptake and reduces the expression of GH-regulated genes directly in skeletal muscle; 2) this supports the concept that somatostatin suppresses GH activity in peripheral tissues, and 3) this may add to the therapeutic effects of somataostatin analogs.
有证据表明，生长抑素不仅能抑制 GH 的分泌，还能抑制外周组织中 GH 的作用。
我们检验了这样一个假设，即生长抑素会抑制人体骨骼肌中的 GH 活性。
8 名健康的年轻男性（25.3±2.8 岁）在禁食过夜 4 小时后进行了单次研究[包括基础期（0-2 小时）和高胰岛素正常血糖钳夹（2-4 小时）]，在此期间进行静脉内 GH 输注（50ng/kg-1·min-1）。每位受试者在一条股动脉内输注生长抑素（150μg/h-1），在对侧股动脉内输注生理盐水。同时从两条股静脉采血。在 t=0 时从一条腿和基础期和钳夹期时从两条腿获取肌肉活检。
肌肉葡萄糖摄取、GH（磷酸化信号转导子和转录激活子 5）和胰岛素（AS160 磷酸化）的信号蛋白，以及 GH 调节基因（IGF-I 和细胞因子信号转导抑制剂 1-3）的表达。
生长抑素显著增加了基础期的动脉静脉葡萄糖差（P=0.03），但在钳夹期没有增加。生长抑素输注侧的 AS160 磷酸化较生理盐水输注侧有升高趋势（P=0.055）。钳夹活检中，生理盐水输注侧的细胞因子信号转导抑制剂 1 mRNA 的表达显著升高（P=0.024）。
我们得出以下结论：1）在全身 GH 暴露的情况下，生长抑素增加基础葡萄糖摄取并直接减少骨骼肌中 GH 调节基因的表达；2）这支持了生长抑素抑制外周组织中 GH 活性的概念；3）这可能增加生长抑素类似物的治疗效果。
