Jørgensen J O, Rosenfalck A M, Fisker S, Nyholm B, Fineman M S, Schmitz O, Madsbad S, Holst J J, Christiansen J S
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark.
Eur J Endocrinol. 2000 Nov;143(5):593-9. doi: 10.1530/eje.0.1430593.
Hyperinsulinemia in association with GH excess is considered a compensatory response to insulin resistance, but the possibility of alternative insulinotropic mechanisms has not been investigated in vivo. It is also unknown how GH influences the secretion from pancreatic beta-cells of amylin, a peptide which regulates prandial glucose homeostasis and may be linked to development of beta-cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as non-glycosylated amylin, in 24 GH-deficient adults before and after 4 months of GH replacement (daily evening injections of 2 IU GH/m).
Double-blind, placebo-controlled, parallel study.
All participants underwent an oral glucose tolerance test (OGTT) at 0 and 4 months.
A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P=0.02), whereas a non-significant increase occurred in the placebo group (P=0.08). Fasting levels of GIP and amylin did not change significantly after 4 months in either group. The incremental response in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P=0.02) and the response in the placebo group (P=0. 03). The stimulation of GIP secretion following OGTT was similar on all occasions. The OGTT-induced incremental response in non-glycosylated amylin was moderately elevated after GH treatment as compared with placebo (P=0.05). Plasma concentrations of glucose and insulin, both in the fasting state and after the OGTT, were higher after GH treatment, but the ratio between amylin and insulin remained unchanged.
GH-induced hyperinsulinemia is accompanied by proportionate elevations in amylin concentrations and a blunting of gut GLP-1 secretion. The mechanisms underlying the suppression of GLP-1 remain to be elucidated.
高胰岛素血症与生长激素（GH）过量相关，被认为是对胰岛素抵抗的一种代偿反应，但尚未在体内研究其他促胰岛素分泌机制的可能性。GH如何影响胰岛β细胞分泌胰淀素也尚不清楚，胰淀素是一种调节餐后葡萄糖稳态的肽，可能与β细胞功能障碍的发生有关。因此，我们测定了24例生长激素缺乏的成年人在接受4个月GH替代治疗（每晚注射2IU GH/m）前后，两种肠道促胰岛素激素即胰高血糖素样肽1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）以及总胰淀素和非糖基化胰淀素的血浆浓度。
双盲、安慰剂对照、平行研究。
所有参与者在0个月和4个月时均接受口服葡萄糖耐量试验（OGTT）。
GH组在4个月时测得空腹GLP-1浓度抑制了33%（P=0.02），而安慰剂组出现非显著性升高（P=0.08）。两组在4个月后GIP和胰淀素的空腹水平均无显著变化。与基线相比，GH治疗后OGTT期间GLP-1的增量反应显著降低（P=0.02），与安慰剂组的反应相比也显著降低（P=0.03）。OGTT后GIP分泌的刺激在所有情况下均相似。与安慰剂相比，GH治疗后OGTT诱导的非糖基化胰淀素的增量反应中度升高（P=0.05）。GH治疗后，空腹状态和OGTT后的葡萄糖和胰岛素血浆浓度均升高，但胰淀素与胰岛素的比值保持不变。
GH诱导的高胰岛素血症伴随着胰淀素浓度的相应升高和肠道GLP-1分泌的减弱。GLP-1抑制的潜在机制仍有待阐明。
