GIP's effect on bone metabolism is reduced by the selective GIP receptor antagonist GIP(3-30)NH2
GIP's effect on bone metabolism is reduced by the selective GIP receptor antagonist GIP(3-30)NH2
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DOI：
10.1016/j.bone.2019.115079
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发表时间：
2020-01-01
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：
Gasbjerg, Laerke S.;Hartmann, Bolette;Knop, Filip K.
肠促胰岛素激素葡萄糖依赖性促胰岛素多肽（GIP）的输注可抑制骨吸收标志物羧基末端1型胶原交联（CTX）。使用选择性GIP受体（GIPR）拮抗剂GIP（3-30）NH 2和GIP的单独和组合输注，我们研究了GIPR抑制如何影响骨转换标志物。（中位年龄22.5岁（范围21-25），BMI 21.3 kg/m（2）（19.9-24.7））参加了一项随机、双盲、安慰剂对照、交叉研究，在四个不同的研究日使用四次1小时12 mmol/l高血糖钳夹，同时输注GIP，GIP + GIP（3-30）NH 2、GIP（3-30）NH 2和安慰剂，间隔至少一周。GIP以1.5 pmol/kg/min输注，GIP（3-30）NH 2以800 pmol/kg/min输注。血糖钳制在12.0 +/- 1.2 mmol/l，GIP和GIP（3-30）NH 2的血浆水平分别接近80 pmol/l和50 nmol/l。GIP对CTX的抑制作用强于安慰剂（减去基线的AUC -6，811 +/-1，260 vs. -3，012 +/-3，018 ng/lx min，P = 0.002），并分别导致CTX值为基线的53 +/- 6.9%（GIP）vs. 81 +/- 10%（安慰剂）（P = 0.0006），在高血糖钳夹结束时。GIP和GIP（3-30）NH 2的共输注使GIP诱导的CTX抑制减弱了51 +/- 33%（P = 0.01）。骨形成标志物1型前胶原N端前肽（P1 NP）的峰值在GIP期间达到较高水平（基线的109 +/- 6.7%）比GIP（3-30）NH 2输注期间（101 +/- 8.9%）（P = 0.049）和GIP抑制PTH水平相比，GIP（3-30）NH 2单独总之，用GIP（3-30）NH 2阻断GIPR减少了GIP诱导的CTX和P1 NP反应，表明这些作用是GIPR介导的，并且GIPR拮抗作用可能干扰骨吸收。
Infusion of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) suppresses the bone resorption marker carboxy-terminal type 1 collagen crosslinks (CTX). Using separate and combined infusions of the selective GIP receptor (GIPR) antagonist, GIP(3-30)NH2, and GIP, we investigated how GIPR inhibition affects bone turnover markers.Ten healthy men (median age 22.5 years (range 21-25), BMI 21.3 kg/m(2) (19.9-24.7)) participated in a randomized, doubled blinded, placebo-controlled, crossover study with four 1 h 12 mmol/l-hyperglycemic clamps on four separate study days with concomitant infusions of GIP, GIP + GIP(3-30)NH2, GIP(3-30)NH2, and placebo, respectively, separated by a period of at least one week. GIP was infused at 1.5 pmol/kg/min and GIP(3-30)NH2 at 800 pmol/kg/min. Plasma glucose was clamped at 12.0 +/- 1.2 mmol/l and plasma levels of GIP and GIP(3-30)NH2 amounted to similar to 80 pmol/l and similar to 50 nmol/l, respectively. GIP suppressed CTX more than placebo (baseline-subtracted AUC - 6,811 +/- 1,260 vs. - 3,012 +/- 3,018 ng/I x min, P = 0.002) and resulted in CTX values of 53 +/- 6.9% (GIP) versus 81 +/- 10% of baseline (placebo), respectively (P = 0.0006), at the end of the hyperglycemic clamp. Co-infusion of GIP and GIP(3-30)NH2 attenuated the GIP-induced CTX suppression by 51 +/- 33% (P = 0.01). The peak value of the bone formation marker N-terminal propeptide of type 1 procollagen (P1NP) peaked at higher levels during GIP (109 +/- 6.7% of baseline) than during GIP(3-30)NH2 infusion (101 +/- 8.9%) (P = 0.049) and GIP suppressed PTH levels compared to GIP(3-30)NH2 alone (P = 0.0158).In conclusion, blockade of the GIPR with GIP(3-30)NH2 diminished GIP-induced CTX and P1NP responses, showing that these effects are GIPR-mediated and that GIPR antagonism might interfere with bone resorption.