Novo Nordisk Foundation Center for Basic Metabolic Research (A.N., F.K.K., J.J.H., B.H.), Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; and Center for Diabetes Research (M.C., F.K.K., T.V.), Department of Medicine, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark.
J Clin Endocrinol Metab. 2014 Nov;99(11):E2325-9. doi: 10.1210/jc.2014-2547. Epub 2014 Aug 21.
In humans, the pronounced postprandial reduction in bone resorption (decreasing bone resorption markers by around 50%) has been suggested to be caused by gut hormones. Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone secreted postprandially from the small intestine. The hormone is known as an incretin hormone, but preclinical studies have suggested that it may also influence bone metabolism, showing both antiresorptive and anabolic effects as reflected by changes in biomechanical measures, microarchitecture, and activity of the bone cells in response to GIP stimulation. Its role in human bone homeostasis, however, is unknown.
To examine the effect of GIP administration on bone resorption in humans.
Plasma samples were obtained from 10 healthy subjects during four conditions: euglycemic (5 mmol/L) and hyperglycemic (12 mmol/L) 90-minute glucose clamps with co-infusion of GIP (4 pmol/kg/min for 15 min, followed by 2 pmol/kg/min for 45 min) or placebo. The samples were analyzed for concentrations of degradation products of C-terminal telopeptide of type I collagen (CTX), a bone resorption marker. RESULTS regarding effects on pancreatic hormone secretion have been published.
During euglycemia, the decremental area under the curve in CTX was significantly (P < .001) higher during GIP infusion (2084 ± 686 % × min) compared to saline infusion (656 ± 295 % × min). During hyperglycemia, GIP infusion significantly (P < .001) augmented the decremental area under the curve to 2785 ± 446 % × minutes, compared to 1308 ± 448 % × minutes during saline infusion, with CTX values corresponding to 49% of basal values.
We conclude that GIP reduces bone resorption in humans, interacting with a possible effect of hyperglycemia.
在人类中，餐后明显的骨吸收减少（通过降低约 50%的骨吸收标志物）被认为是由肠道激素引起的。葡萄糖依赖性胰岛素释放肽（GIP）是一种在餐后从小肠分泌的肽类激素。这种激素被称为肠促胰岛素，但临床前研究表明，它也可能影响骨代谢，通过对 GIP 刺激的生物力学测量、微观结构和骨细胞活性的变化，表现出抗吸收和合成代谢作用。然而，它在人类骨稳态中的作用尚不清楚。
研究 GIP 给药对人类骨吸收的影响。
在 10 名健康受试者的四个条件下获得血浆样本：正常血糖（5 mmol/L）和高血糖（12 mmol/L）90 分钟葡萄糖钳夹，同时输注 GIP（4 pmol/kg/min 持续 15 分钟，然后 2 pmol/kg/min 持续 45 分钟）或安慰剂。分析了 I 型胶原 C 端肽降解产物（CTX）的浓度，CTX 是一种骨吸收标志物。关于对胰腺激素分泌影响的结果已经发表。
在正常血糖期间，GIP 输注时 CTX 的曲线下递减面积明显（P <.001）高于盐水输注时（2084 ± 686%×min 与 656 ± 295%×min）。在高血糖期间，GIP 输注显著（P <.001）增加了 CTX 的曲线下递减面积，达到 2785 ± 446%×分钟，而盐水输注时为 1308 ± 448%×分钟，CTX 值对应于基础值的 49%。
我们的结论是，GIP 减少了人类的骨吸收，与高血糖的可能影响相互作用。
