Department Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand.
Centre for Brain Research, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand.
J Biol Regul Homeost Agents. 2018 May-Jun;32(3):465-478.
Cyclic Glycine-Proline (cGP) regulates the homeostasis of insulin-like growth factor (IGF)-1 function and cGP/IGF-1 ratio determines IGF-1 bioactivity in vitro and in vivo. Plasma IGF-1 represents largely inactive IGF-1 and weakly associated with human obesity and hypertension. We evaluated the regulatory role for cGP in pregnancy-related obesity and hypertension, and in obesity status between pregnancy and postpartum. Women were recruited in their first pregnancy. A cross-sectional study compared plasma concentration of cGP, IGF-1 and IGF binding protein (IGFBP)-3 in women with obesity and/or hypertension to normal controls 6-year postpartum using UPLC-MS and ELISA. A longitudinal study compared the changes of these peptides from 15-week gestation to 6-year post-partum in the women who remained normal weight, remained obese or changed to obese or to normal respectively. Study 1 is a cross-sectional study. The obese group had lower IGF-1(p = 0.001), higher cGP/IGF-1 ratio (p = 0.0055) and the hypertensive group had lower IGFBP-3 (p = 0.046) and cGP (p = 0.043) than the controls. Study 2 is a longitudinal study. Women with weight loss had increased cGP/IGF-1 ratio (p = 0.0026) and decreased IGFBP-3 (p = 0.0001) compared with women whose weight remained normal. Women with weight gain had lower IGFBP-3 (p less than 0.0001) only. Women who remained obese had increased cGP/IGF-1 ratio (p = 0.006) only. Increase in cGP/IGF-1 ratio is associated with obesity, but not hypertension. Changes of IGFBP-3 and/or cGP/IGF-1 ratio are associated with weight changes. The data suggest the role for cGP in obesity through autocrine regulation of IGF-1.
环甘氨酸-脯氨酸 (cGP) 调节胰岛素样生长因子 (IGF)-1 的稳态，cGP/IGF-1 比值决定 IGF-1 的体外和体内生物活性。血浆 IGF-1 主要代表无活性的 IGF-1，与人类肥胖和高血压的相关性较弱。我们评估了 cGP 在妊娠相关肥胖和高血压以及妊娠前后肥胖状态中的调节作用。招募的女性处于第一次妊娠。使用 UPLC-MS 和 ELISA，一项横断面研究比较了 6 年后肥胖和/或高血压女性与正常对照者血浆中环甘氨酸-脯氨酸、IGF-1 和 IGF 结合蛋白 (IGFBP)-3 的浓度。一项纵向研究比较了这些肽从 15 周妊娠到 6 年产后的变化，这些女性分别保持正常体重、保持肥胖或变为肥胖或恢复正常体重。研究 1 为横断面研究。肥胖组 IGF-1 水平较低 (p = 0.001)，cGP/IGF-1 比值较高 (p = 0.0055)，高血压组 IGFBP-3 水平较低 (p = 0.046)和 cGP 水平较低 (p = 0.043)。研究 2 为纵向研究。与体重保持正常的女性相比，体重减轻的女性 cGP/IGF-1 比值增加 (p = 0.0026)，IGFBP-3 减少 (p = 0.0001)。体重增加的女性 IGFBP-3 仅减少 (p 小于 0.0001)。一直肥胖的女性 cGP/IGF-1 比值增加 (p = 0.006)。cGP/IGF-1 比值的增加与肥胖有关，但与高血压无关。IGFBP-3 和/或 cGP/IGF-1 比值的变化与体重变化有关。数据表明 cGP 通过 IGF-1 的自分泌调节在肥胖中起作用。
