Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: Relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures
Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: Relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures
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DOI：
10.1210/jc.82.5.1484
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发表时间：
1997-05-01
影响因子：
5.8
通讯作者：
Unterman, TG
中科院分区：
文献类型：
--
作者：
Benbassat, CA;Maki, KC;Unterman, TG
GH 分泌减少和胰岛素样生长因子 I (IGF-I) 产生减少会导致人类衰老过程中身体成分的改变。 IGF 结合蛋白 (IGFBP) 是 IGF 作用的重要调节剂，但人们对其在衰老中的作用和调节知之甚少。因此，我们测量了 IGFBP-1（一种被胰岛素抑制的 IGF 生物利用度的重要短期调节剂）的水平和 IGFBP-3（主要循环 IGF 载体蛋白）的水平，并检查了它们与胰岛素、葡萄糖、IGF 和硫酸脱氢表雄酮水平以及老年人（63-89 岁）和年轻人的人体测量值的关系。 (23-39岁)男性。老年人的IGFBP-1血清水平增加了3倍。尽管年长者的胰岛素水平较高，但年轻人仍然如此。然而，老年男性和年轻男性的 IGFBP-1 和胰岛素水平相关（r = -0.49；P < 0.002 和 r = -0.42；P < 0.025），表明胰岛素在衰老过程中 IGFBP-1 的调节中继续发挥重要作用。在老年和年轻男性中，血糖水平也与 IGFBP-1 显着负相关（r = -0.37；P = 0.02 和 r = -0.49；P < 0.01），并且这种关系不能用胰岛素的作用来解释。老年人中 IGF-I 水平仅降低了 33% (P < 0.001)，并且与老年男性中的 IGFBP-1 水平相关 (r = -0.40; P < 0.01)，但与年轻男性无关，表明 GH 分泌和/或 IGF-I 产生量低可能导致衰老过程中 IGFBP-1 水平升高。老年人中 IGFBP-3 水平降低，但程度不及年轻人。 IGF-I，导致老年人 IGFBP-3 相对过量（IGPBP-3/IGF-I 比率，20.1 +/- 0.9 cs. 15.4 +/- 1.0；P < 0.001）。 IGFBP-3/IGF-I 比率与年轻和老年男性的 IGF-I 水平相关（r = -0.79；P < 0.001 和 r = -0.82：P < 0.001），表明 GH 分泌减少也可能导致老年人 IGFBP-3 相对过量。老年人的硫酸脱氢表雄酮水平较低。但与任一年龄组的 IGF、IGFBP、胰岛素或葡萄糖水平均不相关。老年人中 IGFBP-1（但不包括 IGF-I、-II 或 IGFBP-3）的血清水平与体重指数以及上臂脂肪和肌肉面积相关。这些关系是由胰岛素的作用解释的，表明胰岛素对 IGFBP-1 的调节可能在决定衰老过程中的身体成分中发挥作用。我们的结论是，胰岛素仍然是老年人 IGFBP-1 水平的重要决定因素，空腹血糖水平也是老年和年轻受试者 IGFBP-1 的重要决定因素，GH 分泌减少可能导致身体成分受损。 通过多种机制参与衰老过程中的合成代谢，包括 IGF-1 产生的减少以及 IGFBP-1 和 -3 循环水平的改变。这些发现与 IGFBP 水平的变化可能导致衰老过程中 TGF 生物利用度和身体成分变化的概念相一致。
Reduced secretion of GH and production of insulin-like growth factor I (IGF-I) contribute to altered body composition in human aging. IGF-binding proteins (IGFBPs) are important modulators of IGF action, yet little is known regarding their role and regulation in aging. Accordingly, we measured levels of IGFBP-1, an important short term modulator of IGF bioavailability that is suppressed by insulin, and levels of IGFBP-3, the major circulating IGF carrier protein, and examined their relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures in old (63-89 yr) and young (23-39 yr) men.Serum levers of IGFBP-1 were increased 3-fold in old cs. young men despite high insulin levels in elders. Nevertheless, IGFBP-1 and insulin levels correlated in old and young men (r = -0.49; P < 0.002 and r = -0.42; P < 0.025), suggesting that insulin continues to play an important role in the regulation of IGFBP-1 in aging. Glucose level also were significantly inversely related to IGFBP-1 in old and young men (r = -0.37; P = 0.02 and r = -0.49; P < 0.01), and this relationship was not accounted for by the effect of insulin. IGF-I levels mere reduced by 33% in elders (P < 0.001) and correlated with IGFBP-1 levels among old (r = -0.40; P < 0.01), but not young, men, indicating that low GH secretion and/or IGF-I production may contribute to the elevation of IGFBP-1 levels in aging.IGFBP-3 levels were reduced among elders, but not to the same extent as IGF-I, resulting in a relative excess of IGFBP-3 in elders (IGPBP-3/IGF-I ratio, 20.1 +/- 0.9 cs. 15.4 +/- 1.0; P < 0.001). The IGFBP-3/IGF-I ratio correlated with IGF-I levels in young and old men (r = -0.79; P < 0.001 and r = -0.82: P < 0.001), indicating that diminished GH secretion also may contribute to a relative excess of IGFBP-3 among elders. Dehydroepiandrosterone sulfate levels were low in elders. but did not correlate with IGF, IGFBP, insulin, or glucose levels in either age group.Serum levels of IGFBP-1 (but not IGF-I or -II or IGFBP-3) correlated with body mass index and upper arm fat and muscle areas in elders. These relationships were accounted for by the effects of insulin, suggesting that regulation of IGFBP-1 by insulin may play a role in determining body composition in aging.We conclude that insulin remains an important determinant of IGFBP-1 levels in elders, that the fasting glucose level is also a significant determinant of IGFBP-1 in both old and young subjects, and that reduced secretion of GH may contribute to impaired anabolism in aging through multiple mechanisms, including reduced production of IGF-1 and alterations in circulating levels of both IGFBP-1 and -3. These findings are consistent with the concept that alterations in IGFBP levels may contribute to changes in TGF bioavailability and body composition in aging.