Role of gastrointestinal hormones in postprandial reduction of bone resorption
Role of gastrointestinal hormones in postprandial reduction of bone resorption
复制标题
DOI：
10.1359/jbmr.2003.18.12.2180
复制
发表时间：
2003-12-01
影响因子：
6.2
通讯作者：
Christiansen, C
中科院分区：
文献类型：
--
作者：
Henriksen, DB;Alexandersen, P;Christiansen, C
引言：血清（s-CTX）中测得的I型胶原C末端肽区可用于评估骨吸收。这种骨吸收的标志物具有受食物摄入影响的显著昼夜变化。材料与方法：我们研究了胃肠道激素葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-2（GLP-2）的释放（GLP-2;肠胰高血糖素原衍生肽的代表）摄入葡萄糖、脂肪、蛋白质和果糖后，以及它们在肠胃外给药后对健康志愿者骨转换过程的影响。此外，我们研究了四种不同剂量的GLP-2单次皮下注射对骨转换的影响（100、200、400或800 μ g GLP-2）或安慰剂治疗60例绝经后女性（平均年龄61 ± 5岁）。如通过s-CTX（从基线的39-52%）评估的，所有大量营养素显著（p < 0.05）降低骨吸收，并且仅胰高血糖素样肽平行分泌。GIP和GLP-1的肠胃外给药没有导致s-CTX水平的降低，而GLP-2与安慰剂相比导致s-CTX水平从基线的统计学显著和剂量依赖性降低（p < 0.05）。在800 μ g GLP-2组中，尿DPD/肌酐（骨吸收的标志物）从基线显著降低了25%（p < 0.01）。GLP-2注射后s-CTX的曲线下面积（AUC（0-8h））分析证实了剂量依赖性降低（ANOVA，p = 0.05）。的s-骨钙素水平是不受GLP-2 treatment.Conclusion：这些研究排除了GIP和GLP-1作为关键介质的立即减少骨吸收后看到的一餐。皮下注射GLP-2后发现骨吸收标志物的剂量依赖性降低，这保证了进一步研究GLP-2对骨转换过程的机制和重要性。
Introduction: The C-terminal telopeptide region of type I collagen as measured in serum (s-CTX) can be used to assess bone resorption. This marker of bone resorption has a significant circadian variation that is influenced by food intake. However, the mediator of this variation has not been identified.Materials and Methods: We studied the release of the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2; a representative of the intestinal proglucagon-derived peptides) after ingestion of glucose, fat, protein, and fructose, as well as their effects after parenteral administration in relation to bone turnover processes in healthy volunteers. Furthermore, we studied the effect on bone turnover of a single subcutaneous injection of GLP-2 in four different dosages (100, 200, 400, or 800 mug GLP-2) or placebo in 60 postmenopausal women (mean age, 61 +/- 5 years).Results: All macronutrients significantly (p < 0.05) reduced bone resorption as assessed by s-CTX (39-52% from baseline), and only the glucagon-like peptides were secreted in parallel. Parenteral administration of GIP and GLP-1 did not result in a reduction of the s-CTX level, whereas GLP-2 caused a statistically significant and dose-dependent reduction in the s-CTX level from baseline compared with placebo (p < 0.05). Urine DPD/creatinine, a marker of bone resorption, was significantly reduced by 25% from baseline in the 800-mug GLP-2 group (p < 0.01). An area under the curve (AUC(0-8h)) analysis for s-CTX after GLP-2 injection confirmed the dose-dependent decrease (ANOVA, p = 0.05). The s-osteocalcin level was unaffected by the GLP-2 treatment.Conclusion: These studies exclude both GIP and GLP-1 as key mediators for the immediate reduction in bone resorption seen after a meal. The dose-dependent reduction of bone resorption markers found after subcutaneous injection of GLP-2 warrants further investigation into the mechanism and importance of GLP-2 for the bone turnover processes.