The role of endogenous GIP and GLP-1 in postprandial bone homeostasis
The role of endogenous GIP and GLP-1 in postprandial bone homeostasis
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DOI：
10.1016/j.bone.2020.115553
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发表时间：
2020-11-01
期刊：
影响因子：
4.1
通讯作者：
Knop, Filip K.
中科院分区：
文献类型：
--
作者：
Helsted, Mads M.;Gasbjerg, Laerke S.;Knop, Filip K.
胰岛素样激素葡萄糖依赖的促胰岛素多肽(GIP)和类胰升糖素多肽1(GLP-1)是众所周知的促胰岛素作用，它们被认为是所谓的肠骨轴的介体，影响骨的动态平衡。在两个随机双盲交叉研究中，我们分别考察了内源性GIP和GLP-1对健康受试者餐后骨稳态的影响。健康男性接受了四次口服葡萄糖耐量试验(OGTTS)(n=18，中位年龄27(范围20-70)，BMI 27.2(22.4-37.0)kg/m(2))或液体混合餐试验(MMTs)(n=12，年龄23(19-65)，体重指数23.7(20.3-25.5)kg/m(2)，输注1)GIP受体拮抗剂GIP(3-30)NH2，2)GLP-1受体拮抗剂Exendin(9-39)NH2，3)GIP(3-30)NH2和Exendin(9-39)NH2，或4)安慰剂输注(生理盐水)。骨吸收由循环羧基末端胶原交联物(CTX)水平和骨形成由前胶原1型氨基末端前肽(P1NP)水平评价。在安慰剂输注期间，CTX曲线下的基线减去面积分别为-39+/-5.0(OGTT)和-57+/-4.3 ng/mlxmin(MMT)。当给予GIP(3-30)NH2时，CTX抑制与安慰剂(-30+/-4.8x min)和-45+/-4.6 ng/mlxmin(MMT)相比显著降低，分别为P=0.0104和P=0.0288。输注Exendin(9-39)NH2时，OGTT/MMT对CTX的抑制作用与安慰剂相似(P=0.28(OGTT)和P=0.93(MMT))。在OGTT和MMT期间，内源性GIP对餐后骨吸收抑制的相对贡献相似，达到22-25%。结论：内源性GIP对人类餐后骨吸收抑制的贡献率高达25%，而内源性GLP-1的作用不明显。
The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are well known for their insulinotropic effects and they are thought to affect bone homeostasis as mediators in the so-called entero-osseous axis. We examined the contributions of endogenous GIP and GLP-1, respectively, to postprandial bone homeostasis, in healthy subjects in two randomized and double-blind crossover studies.We included healthy men who received either four oral glucose tolerance tests (OGTTs) (n = 18, median age 27 (range 20-70), BMI 27.2 (22.4-37.0) kg/m(2)) or liquid mixed meal tests (MMTs) (n = 12, age 23 (19-65), BMI 23.7 (20.3-25.5) kg/m(2)) with infusions of 1) the GIP receptor antagonist GIP(3-30)NH2, 2) the GLP-1 receptor antagonist exendin(9-39)NH2, 3) both GIP(3-30)NH2 and exendin(9-39)NH2, or 4) placebo infusions (saline) on four separate visits. Bone resorption was evaluated from levels of circulating carboxy-terminal collagen cross-links (CTX) and bone formation from levels of procollagen type 1 amino-terminal propeptide (P1NP).During placebo infusions, baseline-subtracted area under the curve values for CTX were - 39 +/- 5.0 (OGTT) and -57 +/- 4.3 ng/ml x min (MMT). When GIP(3-30)NH2 was administered, CTX suppression was significantly diminished compared to placebo (- 30 +/- 4.8 (OGTT) and - 45 +/- 4.6 ng/ml x min (MMT), P = 0.0104 and P = 0.0288, respectively, compared to placebo. During exendin(9-39)NH2 infusion, CTX suppression after OGTT/MMT was similar to placebo (P = 0.28 (OGTT) and P = 0.93 (MMT)). The relative contribution of endogenous GIP to postprandial suppression of bone resorption during both OGTT and MMT was similar and reached 22-25%. There were no differences in P1NP concentrations between interventions.In conclusion, endogenous GIP contributes by up to 25% to postprandial suppression of bone resorption in humans whereas an effect of endogenous GLP-1 could not be demonstrated.