Young S C, Underwood L E, Celniker A, Clemmons D R
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill 27599.
J Clin Endocrinol Metab. 1992 Aug;75(2):603-8. doi: 10.1210/jcem.75.2.1379258.
To determine the effects of exogenous insulin-like growth factor-I (IGF-I) and GH on IGF-binding proteins (IGFBP)-1, -2, and -3, six healthy nonobese adult volunteers underwent two 2-week periods of diet restriction (20 Cal/kg.day), and during the last 6 days of the first period received either IGF-I (12 micrograms/kg.h by iv infusion over 16 h) or GH (0.05 mg/kg.day by sc injection). During the second 2-week study period, the alternate hormone was given. IGFBP-1 and -2 concentrations were determined by specific RIA, and changes in IGFBP-3 were assessed by ligand blotting. Free IGF-I concentrations were measured by size-exclusion high pressure liquid chromatography, followed by RIA. Diet restriction alone did not affect either IGFBP-1 or -2 significantly. IGF-I treatment increased IGFBP-1 from 78 +/- 46 ng/mL (mean pretreatment) to 137 +/- 64 ng/mL (P less than 0.001; mean for the last 4 days of IGF-I). IGF-I also caused an increase in IGFBP-2 from 315 +/- 136 to 675 +/- 304 ng/mL (P less than 0.001). GH injections caused a modest decline in IGFBP-1 concentrations but had no effect on IGFBP-2 concentrations. By ligand blotting, both IGF-I and GH caused a modest increase in IGFBP-3 band intensity. In three subjects diet restriction alone caused a small decrease in IGFBP-3 hand intensity, and this was reversed by hormone treatment. Free IGF-I concentrations in serum were increased from 1.6% to 4.4% of the total IGF-I during IGF-I infusions. GH injections caused a smaller increase in free IGF-I concentrations. The results show significant increases in IGFBP-1 and -2 during IGF-I infusion. The change in IGFBP-3, while significant, is quantitatively less than that in experimental animals that have been given IGF-I while undergoing dietary restriction. The net effect of the changes in these three forms of IGFBPs is not sufficient to maintain a normal IGF-I-binding capacity in serum, because free IGF-I levels were increased disproportionately during the IGF-I infusions. Because hypoglycemia was noted in these subjects despite insulin suppression, these alterations in IGFBPs might have changed the tissue bioavailability of IGF-I and facilitated its hypoglycemic effects.
为确定外源性胰岛素样生长因子-I（IGF-I）和生长激素（GH）对IGF结合蛋白（IGFBP）-1、-2和-3的影响，6名健康的非肥胖成年志愿者经历了两个为期2周的饮食限制期（20千卡/千克·天），在第一个时期的最后6天，分别接受IGF-I（16小时内静脉输注，12微克/千克·小时）或GH（皮下注射，0.05毫克/千克·天）。在第二个为期2周的研究期，给予另一种激素。通过特异性放射免疫分析法（RIA）测定IGFBP-1和-2的浓度，通过配体印迹法评估IGFBP-3的变化。通过尺寸排阻高压液相色谱法，随后进行RIA测定游离IGF-I的浓度。单独的饮食限制对IGFBP-1或-2均无显著影响。IGF-I治疗使IGFBP-1从78±46纳克/毫升（预处理均值）增至137±64纳克/毫升（P<0.001；IGF-I治疗最后4天的均值）。IGF-I还使IGFBP-2从315±136增至675±304纳克/毫升（P<0.001）。GH注射使IGFBP-1浓度适度下降，但对IGFBP-2浓度无影响。通过配体印迹法，IGF-I和GH均使IGFBP-3条带强度适度增加。在3名受试者中，单独的饮食限制使IGFBP-3条带强度略有下降，而激素治疗使其逆转。IGF-I输注期间，血清中游离IGF-I浓度从总IGF-I的1.6%增至4.4%。GH注射使游离IGF-I浓度升高幅度较小。结果显示，IGF-I输注期间IGFBP-1和-2显著增加。IGFBP-3的变化虽显著，但在数量上小于饮食限制期间给予IGF-I的实验动物。这三种形式的IGFBP变化的净效应不足以维持血清中正常的IGF-I结合能力，因为在IGF-I输注期间游离IGF-I水平不成比例地增加。由于尽管胰岛素受到抑制，但这些受试者仍出现低血糖，这些IGFBP的改变可能改变了IGF-I的组织生物利用度，并促进了其降血糖作用。
