IGFBP-1在胎鼠生长发育中作用的研究

目的　探讨胰岛素样生长因子结合蛋白 - 1(IGFBP - 1)在正常胎鼠发育和胎鼠宫内发育迟滞(IUGR)发生中的作用。方法　钳夹孕鼠双侧子宫动、静脉 2 0min ,建立胎鼠IUGR模型 ,观察实验组 (IUGR组 )和正常对照组胎鼠血清IGFBP - 1水平与胎鼠血糖水平、生长参数 (身长、体重 )和器官重量 (胎盘、肺、脑、肝重 )的关系。结果　实验组胎鼠的体重、肺、脑、肝依次为 (1.93± 0 .2 3) g ,(0 .39± 0 .0 1) g ,(0 .10± 0 .0 1) g ,和 (0 .18±0 .0 2 )g ;身长为 (2 .70± 0 .16 )cm ,血糖水平为 (42 .49± 9.2 5 )mg/ml均明显低于对照组的 (3.87± 0 .85 )g ,(0 .47± 0 .0 4) g ,(0 .15± 0 .0 2 ) g ,和 (0 .2 2± 0 .0 6 ) g ,(3.6 1± 0 .44 )cm ,血糖 (6 7.31± 7.12 )mg/ml。血清IGFBP - 1(94.99± 16 .0 7)ng/ml较对照组 (33.2± 6 .96 )ng/ml明显升高 (均P <0 .0 1) ,血清IGFBP - 1与胎鼠血糖水平、生长参数、器官重量呈显著负相关 (均P <0 .0 1)。结论　血清IGFBP - 1作为生长抑制因子参与正常胎鼠发育及IUGR的发生。     

难治性肾病综合征患儿生长激素-胰岛素样生长因子轴的变化及意义

目的：观察难治性肾病综合征(RNS)患儿生长激素(GH)-胰岛素样生长因子(IGF)轴的变化及意义。方法：计算26例RNS患儿的身高标准差积分(HtSDS),以双抗放射免疫法和免疫放射法检测血、尿IGFI及其结合蛋白3(IGFBP3)水平和血GH基础值,以同年龄组正常儿童(NC组,n=18)作对照。结果：RNS组血IGFI(152.68±120.95) ng/ml,IGFBP3(2 183.33±1 711.33) ng/ml低于NC组(255.68±46.92) ng/ml,(4 333.87±1 122.00) ng/ml,(P<0.05),尿IGFI(5.32±2.84) ng/mg肌酐,IGFBP3(16.38±8.55) ng/mg肌酐高于NC组(0.90±0.37) ng/mg肌酐,(5.13±1.64) ng/mg肌酐,(P<0.05);RNS组的血GH水平虽低于NC组,但P>0.05。RNS组身高标准差积分(HtSDS)(-0.42±0.75)低于NC组(0.30±0.17),(P<0.05)。结论：RNS患儿存在GHIGF轴的变化,此变化为RNS患儿生长障碍的主要原因之一。     

早期营养干预对宫内生长迟缓大鼠胰岛素样生长因子和小肠发育及生长追赶的影响

目的　探讨早期营养干预对宫内生长迟缓 (IUGR)幼鼠血清胰岛素样生长因子 (IGF)和小肠发育及生长追赶的影响。方法　将 2 4只IUGR新生雌鼠和 8只正常新生雌鼠随机分为 4组 :IUGR模型组 ,IUGR低蛋白组 ,IUGR高蛋白组 ,正常对照组。于生后 4周时检测各组大鼠血清IGF1、胰岛素样生长因子结合蛋白 3(IGFBP3)浓度、体重、身长和小肠重量、长度及肠黏膜组织结构变化。结果　 4周时IUGR高蛋白组血IGF1、IGFBP3和小肠黏膜绒毛高度、吸收表面积均显著高于对照组和IUGR模型组 (P <0 .0 5或P <0 .0 1) ;小肠重量、长度和体重、身长与对照组比较无显著性差异 (P均 >0 .0 5 )。结论　生后头 4周予高蛋白饮食早期营养干预IUGR幼鼠 ,可通过促进小肠发育达到满意的体格生长追赶。血清IGF1是反映生长追赶的灵敏指标     

胰岛素样生长因子结合蛋白7与肿瘤

胰岛素样生长因子结合蛋白7(insulin-like growth factor binding protein 7,IGFBP7)通过与胰岛素样生长因子(insulin-like growth factor,IGF)、胰岛素相结合,延长IGF/胰岛素的半衰期,从而发挥IGF/胰岛素的生物学功能.与其他结合蛋白不同的是,IGFBP7能与胰岛素强有力的结合,从而能够不依赖IGF而发挥功能.IGFBP7在细胞生长、增殖和在肿瘤细胞的黏附、浸润、迁徙及肿瘤血管的形成等方面发挥作用,可能与某种信号传导通路有关.     

急性缺血缺氧对胎鼠血清IGFs水平和宫内发育的影响

为探讨急性缺血缺氧对胎儿血清IGF Ⅰ、 Ⅱ水平的影响和IGFs在胎儿发育中的作用 ,对 2 1只SD孕鼠被随机分为对照组 9只 ,实验组 1 2只。钳夹实验组孕鼠双侧子宫动、静脉 2 0分钟建立胎鼠缺血缺氧模型 ,对照组仅行开腹和关腹术。比较两组胎鼠血清IGFs、血糖水平及生长参数和器官重量。结果显示 ,实验组血清IGF Ⅰ、 Ⅱ及血糖浓度分别为 1 1 7 92± 2 6 58ng ml,2 33 1 9± 33 35ng ml及 41 6 7±5 6 1mg dl,明显低于对照组 (分别为 2 34 43± 70 6 5ng ml,397 74± 2 3 6 9ng ml及 6 6 4± 4 95mg dl,P均 <0 0 0 1 ) ,其生长参数和器官重量亦明显低于对照组 (P均 <0 0 0 1 )。因此 ,宫内短期的急性缺血缺氧即可致胎儿宫内发育迟缓 (IUGR) ;IGFs水平的降低可能是IUGR发生中的重要因素     

川芎嗪对熏烟致宫内发育迟缓胎鼠脑发育的影响

目的：宫内发育迟缓(IUGR)患儿常有脑发育的异常。川芎嗪能改善脑部微循环,已被应用于新生儿缺氧缺血性脑损伤的治疗。被动吸烟法造大鼠IUGR模型,母鼠在孕8～20d给予川芎嗪,了解其对胎鼠宫内发育迟缓及其脑发育的影响,并探讨其作用机理。方法：孕鼠随机分为4组(均n=9):对照组,模型组,小剂量(40mg/kg)川芎嗪治疗组、大剂量(80mg/kg)川芎嗪治疗组。后3组孕鼠予以被动吸烟导致胎鼠宫内发育迟缓。孕21d剖宫取胎,观测胎鼠体重、脑重、肝重、身长及尾长;检测胎鼠脑组织中一氧化氮(NO)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果：对照组、模型组与小剂量、大剂量川芎嗪治疗组胎鼠IUGR发生率分别为3.9%(4/105),55.0%(50/106),11.8%(11/103)和5.4%(5/99)。模型组胎鼠体重(3.1±0.3gvs3.8±0.6g)、脑重(0.144±0.012gvs0.176±0.018g)、肝重(0.29±0.06gvs0.34±0.07g)均较对照组明显降低,差异有显著差异(均P<0.01),小、大剂量川芎嗪治疗组与模型组相比各指标均有所改善。模型组胎鼠脑组织NO(52.4±1.4μmol/gvs43.7±6.7μmol/g)和MDA(273.5±8.5μmol/gvs249.6±6.2μmol/g)水平较对照组明显增高(均P<0.01),而SOD活性比对照组明显降低29.7±2.6U/mgvs36.5±3.9U/mg(P<0.01)。川芎嗪治疗组与模型组相比,MDA水平降低而SOD活性增高(均P<0.01),较模型组进一步增高。结论：川芎嗪可有效防治被动吸烟诱导的胎鼠IUGR及其脑发育障碍,其机制可能与其纠正机体的氧化与抗氧化失衡有关。     

血清胰岛素浓度的变化与肥胖儿童生长关系的探讨

目的探讨单纯性肥胖儿童的生长与其血清胰岛素(Ins)、胰岛素样生长因子 1(IGF 1)、胰岛素样生长因子结合蛋白 3(IGFBP 3)浓度的关系。 方法2004 03中山大学附属二院对31例单纯性肥胖儿童及48例同龄正常儿童的生长参数及空腹Ins、IGF 1、IGFBP 3浓度进行测定,并进行比较及相关性分析。 结果肥胖组血清Ins、IGFBP 3浓度显著高于对照组(P<005,P<001),而两组间IGF 1差异则无显著性意义,血清Ins浓度与BMI、IGFBP 3呈正相关,肥胖儿童身高SDS与1NS、IGF 1正相关。 结论肥胖儿童存在有非生长激素(GH)依赖性生长的代偿机制。其中高胰岛素血症可能参与了这一过程,它既可以通过增加IGFBP 3的合成来间接提高IGF 1的生物活性,又可以直接发挥促生长作用。     

IGF-I及IGFBP-3对生长激素缺乏症患儿诊断及疗效判断的价值

为了探求一次性抽血确诊生长激素缺乏症 (GHD)的方法和寻找一个检测GH治疗效果的可靠而敏感的生化指标 ,分别用RIA法和IRMA法检测25例GHD患儿血清胰岛素样生长因子 -I(IGF -I)、胰岛素样生长因子结合蛋白 -3(IGFBP -3) ,同时进行生长激素 (GH)刺激试验 ;将GHD患儿分为2组 ,完全性缺乏组 (cGHD)及部分缺乏组 (pGHD) ,将2组血清IGF -I、IGFBP -3与年龄、性别配对的正常儿童 (C组 )均值对照 ,并对照不同年龄及不同发育期的50例正常儿童参考范围 ,计算GHD患儿血清IGF -I、IGFBP -3的降低率 ;将IGF -I与GH峰值做相关性分析。用rhGH治疗GHD3个月后将IGF -I增高值 (△IGF -I)与治疗后每年生长速度 (GV)做相关性分析。结果显示 ,GHD组血清IGF -I、IGFBP -3均显著低于正常对照组 ,两组无重叠 ,cGHD组与pGHD组比较 ,两者差异显著 ;IGF -I及IGFBP -3在GHD组及C组均呈显著正相关 ;GHD组血清IGF -I与GH峰值呈显著正相关 (r=0.85,P<0.001) ,回归方程 :y=0.1613 +0.0235x ,由此可根据血清IGF -I测定值求出GH峰值 ;治疗3个月后△IGF -I与治疗后GV呈显著正相关。提示IGF -I、IGFBP -3对GHD患儿的诊断有重要价值 ;GH峰值可根据所测IGF -I由回归方程求出 ,以代替传统的生长激素刺激试验 ;IGF—I是判断rhGH治疗效果的可靠而     

急性缺血缺氧对胎鼠血清IGFs水平和宫内发育的影响

为探讨急性缺血缺氧对胎儿血清IGF-Ⅰ、-Ⅱ水平的影响和IGFs在胎儿发育中的作用,对21只SD孕鼠被随机分为对照组9只,实验组12只.钳夹实验组孕鼠双侧子宫动、静脉20分钟建立胎鼠缺血缺氧模型,对照组仅行开腹和关腹术.比较两组胎鼠血清IGFs、血糖水平及生长参数和器官重量.结果显示,实验组血清IGF-Ⅰ、-Ⅱ及血糖浓度分别为117.92±26.58ng/ml,233.19±33.35ng/ml及41.67±5.61mg/dl,明显低于对照组(分别为234.43±70.65ng/ml,397.74±23.69ng/ml及66.4±4.95mg/dl,P均＜0.001),其生长参数和器官重量亦明显低于对照组(P均＜0.001).因此,宫内短期的急性缺血缺氧即可致胎儿宫内发育迟缓(IUGR);IGFs水平的降低可能是IUGR发生中的重要因素.     

宫内生长迟缓儿脐血瘦素胰岛素生长激素的水平及临床意义

目的：　探讨脐血瘦素、胰岛素、生长激素在胎儿宫内生长迟缓(IUGR)发病中的作用。方法：　采用放射免疫法测定 31例足月IUGR儿(轻度11例,重度20例)和47例足月适于胎龄儿(正常组)脐血瘦素、胰岛素、生长激素水平。结果：　IUGR儿脐血瘦素、胰岛素、生长激素明显低于正常儿,瘦素(5.55±3.79)ng/ml vs (9.47±5.97)ng/ml,胰岛素(9.75± 4.80)mU/L vs (15.59±9.11)mU/L,生长激素(8.71±4.5 4)ng/ml vs (12.77±4.30)ng/ml,(P<0.01),且IUGR儿的不良生长程度越重,三者水平越低。结论：　瘦素、胰岛素、生长激素分泌不足导致内分泌紊乱,形成一个不利于胎儿生长发育的内环境而至胎儿宫内生长迟缓。     

Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II among the IGF binding proteins (IGFBPs) was studied before and during IGF-I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30–35% of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF-I and the decrease in IGF-II were proportional. Similarly, serum concentrations of IGFBP-3 and the acid-labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.     

新生儿缺氧缺血性脑病血清脑脊液中胰岛素样生长因子-Ⅱ水平的变化

目的：很多研究都证实低水平的胰岛素样生长因子-Ⅰ(IGF-Ⅰ)与缺氧缺血性脑损伤的发生有关,认为IGF-Ⅰ具有重要的神经保护作用。胰岛素样生长因子-Ⅱ(IGF-Ⅱ)在结构及功能上与IGF-Ⅰ具有同源性,但对其在脑损伤中的作用尚不明了。该研究通过观察新生儿缺氧缺血性脑病(HIE)血清、脑脊液中IGF-Ⅱ水平的变化,探讨IGF-Ⅱ在新生儿HIE发病机制及预后中的作用。方法：用放射免疫法(RIA)检测41例HIE新生儿在急性期和恢复期血清、脑脊液及10例正常足月新生儿(对照组)血清中IGF-Ⅱ的水平变化。结果：在急性期,轻、中度HIE组血清IGF-Ⅱ分别为203.28±40.09ng/mL,192.33±39.66ng/mL,较对照组的229.38±43.39ng/mL无显著性降低(P>0.05);重度HIE组血清IGF-Ⅱ水平为116.72±39.50ng/mL较轻、中度HIE组及对照组明显降低(P<0.01)。在恢复期,轻、中度HIE组及重度HIE症状恢复组血清中IGF-Ⅱ分别为285.53±49.44ng/mL;278.69±51.34ng/mL;254.08±48.50ng/mL,脑脊液中分别为81.58±9.77ng/mL;78.48±10.44ng/mL;69.42±10.20ng/mL,较急性期时的27.23±7.82ng/mL,23.43±7.79ng/mL,15.05±7.03ng/mL水平明显增高(P<0.01);重度HIE症状未恢复组血清、脑脊液IGF-Ⅱ分别为144.64±46.30ng/mL;25.05±784ng/mL,虽较急性期增高,但差异无显著性意义(P>0.05),且明显低于其他各组的水平(P<0.01)。HIE组血清与脑脊液间的IGF-Ⅱ水平存在明显的正相关关系(r=0.69,P<0.01)。结论：血和脑脊液中IGF-Ⅱ水平的改变与新生儿HIE的发生及转归有关。     

胰岛素样生长因子结合蛋白3在宫内生长受限儿中的甲基化研究

目的：探讨胰岛素样生长因子结合蛋白3（IGFBP3）启动子区甲基化状态在胎儿宫内生长受限（IUGR）中的作用。方法：选取IUGR新生儿50例及正常新生儿30例,应用甲基化特异性PCR（MSP）及高分辨率溶解（HRM）技术检测外周血中IGFBP3基因的甲基化状态。结果：IUGR组中IGFBP3启动子区完全甲基化比例为4%（2/50）,部分甲基化比例为40%（20/50）,未甲基化比例为56%（28/50）;对照组中部分甲基化比例为13%（4/30）,未甲基化比例为87%（26/30）,两组甲基化率差异有统计学意义(P＜0.01)。结论：IGFBP3基因启动子区的甲基化程度与IUGR的发生有关。     

Relationship of insulin-like growth factor-I, insulin-like growth factor binding protein-3, insulin, growth hormone in cord blood and maternal factors with birth height and birthweight

BACKGROUND: To determine whether the following factors are related to birthweight or birth height, we measured insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein (IGFBP)-3, insulin and growth hormone (GH) levels in cord blood and also observed the relationship between birthweight, birth height and maternal factors. METHODS: One hundred and ninety-four cord bloods were collected, 106 from males and 88 from females. Three newborns were small for gestational age (SGA), 168 were appropriate (AGA) and 23 were large (LGA); 21 newborns were preterm and 172 were term. RESULTS: Levels of IGF-I and IGFBP-3, measured by enzyme-linked immunosorbent assay, were significantly lower in preterm babies (35.3 +/- 15.1 and 1025.6 +/- 562.8 ng/mL, respectively) than in term babies (61.6 +/- 39.5 and 1252.6 +/- 403.2 ng/mL, respectively; P < 0.01), but neither insulin nor GH levels, measured by radioimmunoassay, showed any significant difference between the two groups (P > 0.05). Among term babies, IGF-I and IGFBP-3 levels were significantly higher in the LGA group (96.1 +/- 34.1 and 1544.7 +/- 418.1 ng/mL, respectively) than in the AGA group (56.4 +/- 37.6 and 1212.8 +/- 383.4 ng/mL, respectively; P < 0.01). Levels of IGF-I and IGFBP-3 showed significant correlation with birthweight and length, respectively (P < 0.01), although GH and insulin levels did not (P > 0.05). There was a significant correlation between IGF-I and IGFBP-3 levels (P < 0.01, r = 0.64), but IGF-I and IGFBP-3 levels showed no relationship with GH or insulin levels. Birthweight correlated significantly with prepartum maternal weight, maternal weight gain and maternal height (P < 0.05), but birth length correlated significantly only with maternal height (P < 0.05). CONCLUSIONS: Our results suggest that fetal growth depends on fetal levels of IGF-I and IGFBP-3 and maternal factors, not on insulin or GH. Levels of IGF-I and IGFBP-3 may not be regulated by insulin alone, but by the complex interactions between several factors, such as insulin, GH and maternal factors.     

早期不同饮食营养干预对宫内生长迟缓幼鼠生长追赶的影响

目的　探讨生后早期给予不同饮食构成的营养干预对宫内生长迟缓 (IUGR)幼鼠生长追赶的影响。方法　采用孕母饥饿法建立IUGR大鼠模型 ,32只IUGR新生雌鼠和 8只正常新生雌鼠随机分为五组 (每组 8只 ) :①正常对照组 (C组 ) ,②IUGR模型组 (S组 ) ,③IUGR低蛋白组 (SL组 ) ,④IUGR高蛋白组 (SH组 ) ,⑤IUGR高热卡组 (SA组 )。于生后第 4周测定各组幼鼠的血清胰岛素样生长因子 1(IGF1)及其结合蛋白 3(IGFBP3)浓度和体重、身高、小肠重量、长度及小肠绒毛高度 (VH)、隐窝深度 (CD)、吸收表面积 (VSA)、粘膜厚度 (MT)。结果　IUGR高蛋白组血清IGF1、IGFBP3和小肠VH、VSA、MT及体重均高于C组和S组 (P <0 0 5或P <0 0 1) ;小肠重量、长度和身高与C组比较差异无显著意义 (P >0 0 5 )。血清IGF1与IGFBP3、小肠重量、长度和VH、VSA及体重、身高均呈正相关 (均P <0 0 5 )。结论　血清IGF1是反映生长追赶和营养状态的灵敏指标 ,与小肠和体格的生长追赶呈正相关。生后早期予高蛋白饮食组干预效果较佳 ,可通过促进小肠绒毛的发育和增加营养物质吸收表面积而达到满意的生长追赶。     

Effects of recombinant human insulin-like growth factor I administration in adults with growth hormone deficiency

Recombinant human insulin-like growth factor I (IGF-I), 40 μg/kg/body weight, was administered subcutaneously at 08.00 hours to six adult patients with growth hormone deficiency (GHD). The mean maximal IGF-I concentrations were found 2–6 hours after injection. Concentrations then gradually declined, though mean values were still above basal 24 hours after the injection. Only one patient maintained IGF-I levels above the lower normal range throughout 24 hours. There was a significant decrease in mean IGF-II concentrations when measured 4 and 24 hours after injection of IGF-I. The diurnal variations of insulin and IGF binding protein-1 were preserved. There were no side-effects, and blood glucose remained normal. These results show that in patients with low IGF-I levels resulting from GHD, it is necessary to administer IGF-I at intervals of less than 24 hours to obtain IGF-I levels that are within the normal range.     

Insulin, insulin-like growth factors-I and -II and insulin-like growth factor binding protein-3 in newborn serum: association with normal fetal head growth and head circumference

The insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the regulation of fetal weight and length. The aim of our study was to determine the relationship between head circumference at birth and serum levels of IGF-I, IGF-II, IGFBP-3 and insulin in full-term appropriate-for-gestational age (AGA) infants. Serum samples were obtained from 77 singleton full-term neonates, 69 AGA and 8 small-for-gestational age (SGA). The AGA infants were divided into three groups by head circumference: Group 1: < or = 3rd percentile; Group 2: at 50th percentile; Group 3: > or = 97th percentile. Serum levels of IGF-I, IGF-II, IGFBP-3 and insulin were determined with commercial kits and immunometric methods. There were no statistically significant differences in mean serum levels of IGF-I, IGF-II and IGFBP-3 between the groups. A significantly higher mean serum insulin level was noted in the AGA infants with a head circumference > or = 97th percentile compared to those with a head circumference < or = 3rd percentile (4.6 +/- 0.3 vs 3.3 +/- 0.6 microU/ml; p = 0.04), and in AGA infants with a head circumference above the 50th percentile compared to those with a head circumference below the 50th percentile (4.4 +/- 0.4 vs 3.3 +/- 0.3 microU/ml; p = 0.01). AGA infants with a head circumference above or below the 50th percentile did not differ statistically in their mean IGF-II and IGFBP-3 serum level, while IGF-I differed statistically between the groups (18 +/- 2.7 vs 11.6 +/- 1.6 ng/ml, respectively; p = 0.045). Using univariate analysis, head circumference correlated positively with insulin (r = 0.29; p = 0.016) and with IGF-I (r = 0.26; p = 0.03). A stepwise multivariate linear regression analysis, however, did show statistically significant correlation of head circumference with birth weight (f = 36; p = 0.0001), and only marginally with birth length (f = 4.7; p = 0.06) and insulin (f = 3.4; p = 0.07). No correlations were found between head circumference and IGF-I, IGF-II or IGFBP-3. These data suggest that apart from genetic and nutritional factors, insulin may play a role in promoting intrauterine head growth, as reflected by head circumference at birth.     

Serum levels of insulin-like growth factor-I,-II and insulin-like growth factor binding proteins-2 and-3 in children with acute lymphoblastic leukaemia

Abstract The insulin-like growth factor (IGF) signaling pathway may be of importance for the proliferation of different tumours (e.g. breast cancer and Wilms tumour). The bioavailability of both IGF-I and IGF-II is regulated by specific IGF-binding proteins (IGFBPs). IGFBP-2 is the predominant binding protein during fetal life, where it is expressed in most tissues. In contrast, postnatally it is mainly released by specific cell types (hepatocytes, astroglia, kidney cells, prostate cells) and a range of tumour cell lines. Furthermore, phytohaemagglutinin stimulated normal lymphoblasts and malignant lymphoblasts express IGFBP-2. In order to investigate the IGF regulatory pathway in leukaemia serum levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were determined in 28 leukaemic children. Whereas serum levels of IGF-I (mean/range: –2.7/–0.1 to –6.7 SDS), IGF-II (–3.6 SDS/–1.3 to –8.7) and IGFBP-3 (–2.0/+2.2 to –7.1 SDS) were significantly decreased comparable to levels in growth hormone deficiency, IGFBP-2 levels (+4.0/–0.45 to +7.4 SDS) were found to be markedly elevated and inversely correlated to IGF-I (r=–0.51,P=0.013). After haematological remission upon chemotherapy all four parameters had normalized in the 16 re-investigated children. Similar findings have been observed in one boy with a relapse including CNS leukaemia.Conclusion This study demonstrates that the proliferation of malignant lymphoblasts (at diagnosis vs treatment) occurs in the presence of decreased serum levels of IGF-I, IGF-II and IGFBP-3 and that diminished production of these peptides may contribute to impaired growth. It further indicates that serum levels of IGFBP-2 may be directly related to the proliferation of lymphoblasts.     

Secretion of insulin-like growth factor-II into bile of rats of different ages

Bile from rats of different ages (suckling 10-12 days; weanling 30-33 days, and adult 60-70 days) was collected and studied for the presence of immuno- and receptor-assayable insulin-like growth factor-II (IGF-II) concentrations. Concentrations of RIA IGF-II in bile were highest in suckling rats (230 +/- 38 ng/ml) and lowest in adults (47 +/- 7 ng/ml). These concentrations were approximately twice those of the bile IGF-I concentration in sucklings, as measured in a previous study. Selected bile samples were also assayed using a competitive binding assay with a crude preparation of adult rat liver membranes bearing the IGF-II receptor. These studies confirmed the presence of receptor- (as well as immuno-) active IGF-II in bile. Since bile flow rates increased dramatically after the suckling period, bile delivery rates of IGF-II were normalized as picograms per gram body weight per hour. When such calculations were done, bile IGF-II delivery rates to the small intestine were highest in sucklings and weanlings in comparison to adult rats. Thus non-enterically derived (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be approximated at roughly 1 microg/day. Unlike IGF-I, intravenously injected IGF-II could not be detected in suckling bile, suggesting a predominantly hepatic origin. From this study we conclude that there exists a significant delivery of receptor-active IGF-II to the gastrointestinal tract of rats of all ages.