Serum insulin-like growth factor (IGF)-I concentrations are reduced by short-term dietary restriction and restored by refeeding in domestic cats (Felis catus).

Nutritional modulation of insulin-like growth factors (IGF) and their binding proteins (IGFBP) is well established. The effect of nutritional restriction on the serum IGF/IGFBP system of adult cats was investigated to evaluate serum IGF-I as a biochemical marker of nutritional status. Assays for measuring feline serum IGF and IGFBP were validated and normal ranges established in a study population of 46 healthy nonobese adult cats. Serum concentrations of IGF-I and IGF-II correlated significantly with body weight (r = 0.75, P < 0. 0001 and r = 0.34, P < 0.03, respectively). Serum IGFBP profiles were similar to other species, including humans, dogs and guinea pigs. IGFBP-3 was the predominant binding protein reflecting IGF-I concentrations and body size. Serum IGFBP-2 concentrations were high relative to the normal human serum pool (NHS) control. Food withdrawal for 18 h followed by refeeding did not alter circulating IGF or IGFBP concentrations, including IGFBP-1, in nine cats. Short-term dietary restriction of nine adult cats to supply initially 56% (56%M) and then 42.5% (42.5%M) of calculated maintenance energy requirements for 14 d resulted in a significant weight loss (P < 0.01). However, serum IGF-I concentrations fell significantly (-51%, P < 0.01) only with 42.5%M restriction. Serum IGF-II, IGFBP, insulin and albumin concentrations were not altered during the study. We conclude that nutrition does modulate the adult feline IGF/IGFBP system, but to a lesser extent than in other species. Further evaluation is required before serum IGF-I can be used for the assessment of nutritional status in adult cats.     

脐血瘦素及IGF和胰岛素水平与胎儿生长发育相关性研究

目的:探讨脐血瘦素、胰岛素样生长因子(IGF)和胰岛素水平与胎儿生长发育的相关性。方法:采用放射免疫法检测80例足月新生儿脐血瘦素、IGF-I、IGF-II和胰岛素水平,根据胎龄和新生儿出生体重将新生儿分为小于胎龄儿(SGA)、适于胎龄儿(AGA)和大于胎龄儿(LGA)3组,采用新生儿出生时体重、身长和Rohrer's指数估测胎儿生长发育状态。结果:LGA组脐血瘦素、IGF-I和胰岛素水平明显高于AGA组(12.03±1.22vs7.11±1.00,70.21±3.23vs43.48±0.96,4.03±1.12vs3.19±0.92),SGA组脐血瘦素、IGF-I和胰岛素水平明显低于AGA组(2.66±1.03vs 7.11±1.00,22.13±5.98vs43.48±0.96,2.34±3.63vs3.19±0.92);脐血瘦素水平与胎儿出生体重、身长和Rohrer's指数呈显著正相关,LGA和AGA组脐血IGF-I和胰岛素水平与胎儿出生体重、身长和Rohrer's指数呈显著正相关,LGA和AGA组脐血瘦素水平与IGF-I和胰岛素呈显著正相关。结论:脐血瘦素、IGF-I和胰岛素水平与新生儿的体重、身长和Rohrer's指数存在相关性,提示瘦素、IGF-I和胰岛素在胎儿生长发育中起重要作用。     

Response of the insulin-like growth factor system to vitamin A depletion and repletion in rats

Vitamin A (VA) and insulin-like growth factors (IGF) are important regulators of a wide range of physiological processes. To investigate the IGF system's involvement in the physiological actions of VA, we examined the effects of VA status on components of the IGF system in rats. Male rats (3-wk-old) fed a VA-deficient diet for 11 wk developed VA deficiency, as confirmed by the depletion of serum retinol and hepatic retinyl palmitate. Rats fed the VA-deficient diet had significantly lower body weight (p < 0.05) and lower serum IGF-I concentrations than the rats fed the control diet. The decreases in serum IGF-I levels were accompanied by approximately 40% lower levels of the IGF-I mRNA in the liver and lungs. With respect to the gene expression of other IGF system components, VA deficiency caused a twofold induction of IGF-I receptor (IGF-IR) mRNA in the heart and a twofold reduction in IGFBP-6 mRNA in the lungs, but did not alter the expression of IGF-II, IGFBP-1, IGFBP-3, IGFBP-4 or IGFBP-5 in all tissues examined. When VA-deficient rats received a single injection of retinoic acid (2 mg/rat), tissue IGF-I and IGF-IR gene expression did not change after 4 or 8 h, while the expression of IGF-II, IGFBP-4, and IGFBP-6 mRNAs in some tissues increased rapidly. These results suggest a possible involvement of the IGF system in mediating the physiological actions of VA, including VA-supported growth, in the rat.     

Relation of cord serum levels of growth hormone,insulin-like growth factors,insulin-like growth factor binding proteins,leptin, and interleukin-6 with birth weight,birth length,and head circumference in term and preterm neonates

OBJECTIVES: Fetal growth process is governed by multiple factors. We investigated the relation of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), leptin, and interleukin-6 (IL-6) with intrauterine growth in preterm and term neonates. METHODS: Thirty-eight preterm and 43 term neonates were recruited. Anthropometric measures were recorded and umbilical cord blood samples were collected at birth. RESULTS: Birth weight (BW), birth length (BL), ponderal index, head circumference (HC), and cord serum levels of albumin, prealbumin, retinol-binding protein (RBP), total and free IGF-I, IGF-II, IGFBP-3, acid-labile subunit (ALS), and leptin were significantly lower, whereas levels of IGFBP-1, IGFBP-2, and IL-6 were significantly higher in preterm than in term neonates (P < 0.05). Total and free IGF-I, ALS, and leptin had significantly positive correlations, whereas IGFBP-2 had a significantly negative correlation, with BW and BL in preterm plus term neonates. Forward stepwise multivariate regression analysis showed that gestational age (GA), IGFBP-2, leptin, and free IGF-I are significant predictors of BW; GA, IGFBP-2, ALS, transferrin, and leptin are significant predictors of BL; and GA and free IGF-I are significant predictors of HC in preterm and term neonates. CONCLUSIONS: Our results suggest that IGF-I, IGF-II, IGFBP-2, ALS, and leptin play important roles in intrauterine growth.     

Loss of the pregnancy-induced rise in cortisol concentrations in the ewe impairs the fetal insulin-like growth factor axis

Maternal cortisol levels increase during pregnancy. Although this change is important for optimal fetal growth, the mechanisms of the changes in growth remain unclear. The hypothesis examined was that alterations in maternal plasma cortisol concentrations are associated with changes in the fetal insulin-like growth factor (IGF) axis. Pregnant ewes in late gestation (115 ± 0.4 days) were studied: six control animals, five ewes given 1 mg kg(-1) day(-1) cortisol (high cortisol) and five adrenalectomised ewes given 0.5-0.6 mg kg(-1) day(-1) cortisol (low cortisol). Blood samples were taken throughout the experiment and at necropsy (130 ± 0.2 days) and fetal liver was frozen for mRNA analysis. Fetal IGF-I and insulin plasma concentrations were lower and insulin-like growth factor-binding protein-1 (IGFBP-1) concentrations were higher in the low cortisol group compared with those in the control group (P < 0.05). Fetal liver IGF-II and IGFBP-3 mRNA were decreased in low cortisol animals compared with controls (P < 0.05). There were no significant changes in these parameters in the high cortisol group, and there were no changes in fetal liver IGF-I, growth hormone receptor, IGF-I receptor, IGF-II receptor, IGFBP-1 or IGFBP-2 mRNA levels between the groups. These data suggest that reduced fetal IGF availability contributes to reduced fetal growth when maternal cortisol secretion is impaired, but not during exposure to moderate increases in cortisol.     

非营养性吸吮对早产儿血清IGF-1、IGFBP-3及生长发育的影响

目的:探讨非营养性吸吮对早产儿血清IGF-1、IGFBP-3及生长发育的影响。方法:以2008年9月～2009年8月收治的早产儿60例为研究对象,随机分为非营养性吸吮(NNS)组和对照组,采用ELISA法测定生后第1天开奶前及生后第3天、第7天、第14天血清IGF-1、IGFBP-3水平,同时记录生长发育指标(头围、身长)。结果:①NNS组血清IGF-1、IGFBP-3水平在生后第7、14天高于对照组(P<0.05)。②与对照组相比,NNS组第14天头围、体重增长差异有统计学意义(P<0.01)。③血清IGF-1与头围、体重增长呈正相关(r=0.684,P<0.01;r=0.656,P<0.01),与血清IGFBP-3水平呈正相关(r=0.659,P<0.01)。结论:NNS能提高血清IGF-1、IGFBP-3水平,加快早产儿的生长发育。     

Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer

BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). OBJECTIVE: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. DESIGN: We conducted a randomized, placebo-controlled, double-blinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. RESULTS: Lycopene supplementation significantly (P = 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: -5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. CONCLUSIONS: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies.     

Isolated isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk

Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: -1.3%, 95% CI -8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r=-0.49, P=0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies.     

胰岛素样生长因子及其结合蛋白与妊娠期高血压疾病的相关性研究

目的:研究妊娠期高血压疾病患者血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-1(IGFBP-1)的水平与病情程度及新生儿出生体重之间的关系。方法:采用放射免疫方法测定并比较38例妊娠期高血压疾病患者与38例正常血压妊娠妇女的血清IGF-1、IGFBP-1的水平。结果:子痫前期组IGF-1显著低于妊娠期高血压组和正常组,而IGFBP-1水平显著高于妊娠期高血压组和正常组;妊娠期高血压组与正常组间IGF-1、IGFBP-1的水平比较,差异均无统计学意义。IGF-1水平与收缩压、舒张压及平均动脉压呈显著负相关,与新生儿出生体重呈显著正相关,而IGFBP-1与收缩压、舒张压及平均动脉压呈显著正相关,与新生儿出生体重呈显著负相关。结论:妊娠期高血压疾病患者的发病及严重程度与IGF-1、IGFBP-1有明显的关系,IGF-1、IGFBP-1与胎儿的发育及新生儿出生体重有明显的相关性。     

The effect of economic status on height, insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in healthy Turkish children

OBJECTIVES: The effect of economic status (ES) on growth, insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in healthy children is not well characterized. We aimed to study the interrelationship between height, weight, IGF-I, IGFBP-3, mid-parental height (MPH) and ES. DESIGN/SUBJECTS: Eight hundred and fourteen healthy children (428 boys, 386 girls; age 3-18 years) were classified according to income of the families as low, middle and high. Standard deviation scores (SDSs) of height, weight, MPH, IGF-I and IGFBP-3 were compared between the groups. The combined effect of these parameters and ES on height SDS was investigated with complex statistical models. RESULTS: There was a significant trend for height and weight SDSs to increase with higher income levels in boys, but not in girls. Body mass index (BMI) SDSs were similar in three groups. There was a general trend for MPH SDS to increase with income levels in both sexes. In boys, IGF-I SDS was significantly higher in high ES group than low ES. In girls, IGFBP-3 SDSs were significantly higher in high ES group than in middle ES group. For both genders, height SDS was highly correlated with weight SDS and moderately correlated with BMI SDS, MPH SDS and IGF-1 SDS. All correlations were significant and positive. Complex models showed that MPH (19%), IGF-I (13%) and ES (3%) in boys, and MPH (16%) and IGF-I (7%) in girls have significant contribution to height SDSs. CONCLUSIONS: ES per se, independent of overt malnutrition, affects height, weight, IGF-I and IGFBP-3 with some gender differences in healthy children. Influence of income on height and weight show sexual dimorphism, a slight but significant effect is observed only in boys. MPH is the most prominent variable effecting height in healthy children. Higher height and MPH SDSs observed in higher income groups suggest that secular trend in growth still exists, at least in boys, in a country of favorable economic development.     

Maternal concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 1 during pregnancy and birth weight of offspring

Maternal concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 1 (IGFBP-1) may influence fetal growth. Offspring birth weight related to maternal IGF-I and IGFBP-1 measured in pregnancy was studied in 368 randomly selected women without preeclampsia who delivered a singleton liveborn child in Norway between 1992 and 1994. Maternal IGF-I concentrations were not consistently associated with birth weight, but a 1-standard deviation stronger increase in IGF-I from the first to second trimester was associated with an 82-g (95% confidence interval (CI): 11, 153) higher birth weight. IGFBP-1 concentrations were inversely associated with birth weight: Birth weight was 71 g (95% CI: 14, 128) lower per 1-standard deviation higher IGFBP-1 in the second trimester, and an increase in IGFBP-1 from the first (below median) to second (above median) trimester was associated with a 342-g (95% CI: 124, 560) lower birth weight, compared with having low IGFBP-1 (below median) in both trimesters. Conversely, low IGFBP-1 in both trimesters was associated with a 200-350-g higher birth weight compared with other combinations of IGFBP-1. In conclusion, persistently low IGFBP-1 in pregnancy is associated with relatively higher birth weight. Maternal insulin resistance may provide a link between IGFBP-1 and offspring birth weight.     

Correlation between the components of the insulin-like growth factor I system, nutritional status and visceral leishmaniasis

The role of the insulin-like growth factor I (IGF-I) system and nutritional status was studied in 241 children from a Brazilian area endemic for visceral leishmaniasis (VL). Thirty-nine children had the active form, 20 were oligosymptomatic, 38 were asymptomatic and 144 were not infected. Serum concentrations of growth hormone (GH), total and free IGF-I and IGF binding-protein 3 (IGFBP3) were measured by radioimmunoassay. Nutritional status was evaluated by anthropometric indicators and biochemical measurements. Total and free IGF-I and IGFBP3 were significantly reduced in the active form. Z scores for total and free IGF-I and for IGFBP3 were found to be significantly lower for active VL and oligosymptomatic individuals than for asymptomatic individuals, but never reached values 相似文献   

Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk

Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases serum levels of total IGF-I in premenopausal women with 1) a history of breast cancer (n=24) or 2) a high familial breast cancer risk (n=36). Also, IGF binding protein (IGFBP) increasing effects were evaluated. Lycopene supplementation did not significantly alter serum total IGF-I and other IGF system components in the 2 study populations combined. However, statistically significant discordant results were observed between the 2 study populations (i.e., P<0.05 for total IGF-I, free IGF-I, and IGFBP-3). Total IGF-I and IGFBP-3 were increased in the breast cancer survivor population [total IGF-I=7.0%, 95% confidence interval (CI)= -0.2 to 14.3%; IGFBP-3=3.3%, 95% CI=0.7-6.0%), and free IGF-I was decreased in the family history population (-7.6%, 95% CI= -14.6 to -0.6%). This randomized controlled trial shows that 2 mo of lycopene supplementation has no effect on serum total IGF-I in the overall study population. However, lycopene effects were discordant between the 2 study populations showing beneficial effects in high-risk healthy women but not in breast cancer survivors.     

新生儿瘦素水平动态变化与胰岛素样生长因子—Ⅰ、胰岛素及生长激素关系研究

目的:探讨新生儿期血清瘦素、胰岛素样生长因子—Ⅰ(IGF-I)、胰岛素、生长激素水平变化及其对新生儿生长发育的影响。方法:采用放射免疫法检测100例正常足月人工喂养新生儿脐静脉和静脉血瘦素、IGF-I、胰岛素和生长激素水平,并按采血时间分为初生脐血组、早期新生儿组(生后4~6天)和晚期新生儿组(生后25~28天),采用新生儿体重、身长和R I指数评估新生儿生长发育情况。结果:脐血瘦素水平与IGF-I、胰岛素、生长激素水平和出生体重呈正相关,r值分别为0.45、0.374、0.56和0.646(P均<0.01);早期新生儿组血清瘦素水平(0.45±0.38)μg/L显著低于初生脐血组(8.51±5.64)μg/L,其下降值与此期间IGF-I的下降值呈显著正相关(r=0.28),而与胰岛素、生长激素和新生儿体重的下降值无关:晚期新生儿瘦素水平(1.83±0.73)μg/L回升,高于早期新生儿水平(P<0.01),其增长值与血清IGF-I、胰岛素、生长激素以及体重的增长值呈显著正相关,r值分别为0.45、0.384、0.289、0.484(P<0.01~0.05)。结论:新生儿期血清瘦素水平的动态变化与体重、血清IGF-I、胰岛素和生长激素水平有一定相关性,提示瘦素对新生儿期生长发育和能量代谢方面发挥重要作用;瘦素可能通过营养物质—胰岛素—IGF-1—生长激素内分泌轴共同调控新生儿生长发育。     

L-Carnitine changes the levels of insulin-like growth factors (IGFs) and IGF binding proteins in streptozotocin-induced diabetic rat

This study investigated the effects of L-carnitine on insulin-like growth factor-I/II (IGF-I/II) and insulin-like growth factor binding proteins (IGFBPs) in streptozotocin (STZ)-induced diabetic rats. Each rat in the three L-carnitine-treated groups was injected subcutaneously with L-carnitine, 50 (D50), 100 (D100), or 200 (D200) mg/kg body weight every other day for four weeks, and animals in normal (N) and diabetic (DM) groups received saline by the same method. Diabetic rats had significantly lower carnitine concentrations in serum and liver compared with normal rats. Total carnitine concentrations were increased dose-dependently by carnitine treatment. Total IGF-I in serum from diabetic rats was increased dose-dependently by carnitine treatment, but was statistically significant only in the D200 group. The expression of liver IGF-I mRNA was lower in diabetic rats than in normal rats and increased by L-carnitine treatment. L-Carnitine treatment of diabetic rats had no effect on the levels of IGF-II in serum, liver, and kidney. Although the levels of IGF-II in serum and kidney of diabetic rats were increased in comparison with normal rats, IGF-II mRNA was not expressed in liver. Diabetic rats had markedly lower IGFBP-3 than normal rats did, and IGFBP-3 was increased by L-carnitine treatment. These results demonstrate that L-carnitine treatment of diabetic rats modulates the IGFs/IGFBPs axis. Especially note-worthy is that L-carnitine at a dose of 200 mg/kg/48 h for four weeks was able to restore serum total IGF-I in STZ-induced diabetic rats to nearly normal levels.     

血清IGF-1、IGFBP-3水平和大肠癌关系的Meta分析

目的综合评价血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平和大肠癌的关系。方法利用Meta分析法对6篇关于血清IGF-1、IGFBP-3水平与大肠癌关系的研究文献进行定量综合分析。结果对于IGF-1，合并OR=1．56(95％CI：1．14～2．13)；按实验方法不同分层，间接酶联免疫吸附试验(ELISA)合并OR=1．92(95％CI：1．26～2．93)，IRMA法合并OR=1．23(95％CI：0．78～1．94)；对于IGFBP-3，合并OR=0．78(95％CJ：0．43～1．44)；按实验方法不同分层，ELISA法合并OR=0．46(95％CI：0．29～0．74)，免疫放射测定法(IRMA)合并OR=1．44(95％CI：0．93～2．23)。结论血清IGF-1高水平为大肠癌的独立危险因子，IGFBP-3与大肠癌的关联不具有统计学意义；IGFBP-3与大肠癌关系的各研究之间异质性是由实验方法不同而引起，但该结论尚需大样本并同时进行两种方法的测量证实。     

Soy isoflavones do not modulate circulating insulin-like growth factor concentrations in an older population in an intervention trial

Insulin-like growth factors (IGF) are essential for normal growth and maintenance of lean muscle mass; however, high insulin-like growth factor-I (IGF-I) and low IGF binding protein-3 (IGFBP-3) levels are also associated with several cancers. To test the hypothesis that long-term soy isoflavone supplementation decreases circulating IGF-I concentrations, we conducted a controlled, parallel-arm, double-blind intervention study with 150 participants (85% men), 50-80 y old. Participants were randomly assigned to consume a soy beverage powder daily for 12 mo. The active treatment group (+ISO) received soy protein containing 83 mg isoflavones, whereas the comparison group (-ISO) received soy protein containing 3 mg isoflavones. Serum IGF-I and IGFBP-3 were measured by ELISA. Mean change in serum IGF-I concentrations was similar in the two groups (+1.4 nmol/L in +ISO, +1.2 nmol/L in -ISO; P = 0.74, 95% confidence interval -1.1, +1.5 nmol/L for the 0.21 nmol/L difference between groups), indicating no effect of the isoflavone intervention. Similarly, the changes in IGFBP-3 and the IGF-I/IGFBP-3 ratio were similar in both groups, again showing no effect of +ISO treatment. A 12 mo, 83 mg/d soy isoflavone intervention did not modulate serum IGF in an older, mostly male population.     

Epidemiology of the insulin-like growth factor system in three ethnic groups.

The insulin-like growth factor (IGF) system, comprising insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and their binding proteins (IGFBPs), is linked to cell growth, the development of cardiovascular disease, and several cancers. Little is known about its epidemiology. The authors studied relations of the IGF system to anthropometric and metabolic variables in three population-based ethnic groups in Manchester, England, in 1994-1998 with differing disease risks: African Caribbean (n = 193), Pakistani (n = 130), and local Europeans(n = 142). Standardized anthropometry, glucose tolerance tests, and serum assays were performed. Body mass indices (BMIs) were high in all groups. IGF-I levels were highest in normoglycemic African Caribbeans and declined with age (r = -0.28). IGF-II levels were greatest in Europeans. IGFBP-1 concentrations increased with age in Pakistanis (r = 0.20) and Europeans (r = 0.29), but not in African Caribbeans (r = 0.06), and were inversely related to BMI (r = -0.37). Age- and sex-adjusted IGFBP-1 was inversely related to fasting insulin and proinsulin in all groups; participants with newly detected diabetes were relatively insulinopenic but had higher IGFBP-1 concentrations. Nonesterified (free) fatty acid (NEFA) concentrations increased with declining glucose tolerance. In multiple regression analysis, IGFBP-1 was independently and negatively related to fasting insulin, BMI, and African-Caribbean compared with European ethnicity but positively related to age, fasting glucose, and NEFA. IGF-I was inversely related only to age, NEFA, and Pakistani ethnicity. IGF-II showed a strong ethnic difference but was unrelated to other variables. These data indicate considerable potential for exploring disease-IGF system relations in population samples.     

Growth velocity during the first postnatal week of life is linked to a spurt of IGF-I effect

There is adequate evidence that growth during the perinatal period is linked to the risk of several adult onset diseases, and recent findings indicate that the insulin-like growth factor (IGF) system is involved in prenatal growth, as reflected in birthweight. However, whether major components of the IGF system are involved in the immediate post-natal growth has not been studied. Maternal questionnaires were completed, and laboratory measurements of several variables, including IGF-I, IGF-II and IGF-binding protein-3 (IGFBP-3), were made for a total of 331 apparently healthy full-term newborns, from whom routine blood samples were taken during the first 5 days of their life. Birthweight and weight at the time of bleeding were among the recorded variables, and the difference divided by the age in days of the newborn was considered as reflecting immediate postnatal growth velocity. Immediate postnatal growth velocity was strongly positively associated with IGF-I. The squared adjusted correlation coefficient was 0.29 when IGF-I was incorporated in the model predicting postnatal growth velocity but was only 0.08 when IGF-I was excluded. In contrast, IGF-II and IGFBP-3 had no effect on postnatal growth velocity. It thus appears that IGF-I underlies growth during the immediate postnatal period. To the extent that perinatal growth may affect adult onset diseases, the findings of this study suggest that the action of IGF-I during the immediate postnatal period may represent a process of major importance.     

Specific decrease in liver insulin-like growth factor-I and brain insulin-like growth factor-II gene expression in energy-restricted rats.

Four-week-old male rats were maintained for 10 d on a series of diets containing a constant high level of dietary protein and total energy at 100, 70, 60 or 50% of the ad libitum intake rate. Under these conditions, growth rate varied as a function of dietary energy. Serum insulin-like growth factor (IGF)-I was decreased in the energy-restricted animals. Total hepatic IGF-I mRNA was decreased by approximately the same factor as circulating IGF-I protein. In contrast to previous results obtained with protein-restricted animals, serum albumin mRNA was not decreased in the energy-restricted animals. Brain IGF-II mRNA was slightly decreased in animals fed the 70 and 60% energy diets and was decreased by 50% in animals fed the 50% energy diet. Insulin-like growth factor binding protein-2 (IGFBP-2) gene expression was increased in the liver but not in the brain of the energy-restricted animals, indicating that dietary energy regulates IGFBP-2 gene expression differently in liver and brain. The results demonstrate specific changes in liver IGF-I and IGFBP-2 gene expression and brain IGF-II gene expression in animals that are growth-retarded because of a restriction of dietary energy.