学龄前肥胖儿童血清IGF-Ⅰ、IGF-BP_3与其他激素相互关系的研究

【目的】研究学龄前肥胖儿童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（IGF-BP3）与瘦素（Leptin）、胰岛素（Ins）、雌二醇（E2）及睾酮（T）的相互关系,探讨IGF-I在肥胖发病机制中的作用,为肥胖儿童的早期干预提供理论依据。【方法】对122例学龄前肥胖儿童及61例正常儿童血清IGF-Ⅰ、IGF-BP3、Leptin、Ins、E2和T水平进行测定,并分析IGF-Ⅰ、IGF-BP3与其他激素的相互关系。【结果】学龄前肥胖儿童血清IGF-Ⅰ、IGF-BP3、Leptin、Ins和E2水平明显高于对照组（P值均〈0.001）,两组间睾酮水平差异无显著性（P〉0.05）;血清IGF-Ⅰ、IGF-BP3与Leptin、Ins、E2及睾酮水平显著正相关（P值均〈0.01）,且Leptin与Ins、E2水平显著正相关（P值均〈0.001）;多元线性回归分析显示IGF-BP3、Ins和E2是影响IGF-Ⅰ的重要因素。【结论】学龄前肥胖儿童IGF-Ⅰ、Leptin和Ins在调节机体能量代谢过程中不仅作为独立的外周因子发挥作用,同时提示IGF-Ⅰ对儿童生长发育以及性发育的调控受Leptin、Ins及性激素多种激素水平的共同影响,IGF-Ⅰ是儿童肥胖又一敏感检测指标。     

学龄前肥胖儿童体质指数与血清瘦素、胰岛素及性激素水平的关系

[目的]研究学龄前肥胖儿童体质指数与血清瘦素、胰岛素及性激素水平的关系. [方法]对122例学龄前肥胖儿童及61例健康正常儿童的瘦素(Leptin)、胰岛素(Ins)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、胰岛素样生长因子结合蛋白-3(IGF-BP3)、雌二醇(E2)和睾酮(T)水平进行测定,测量其身高、体重.计算其体质指数(body mass index,BMI),并分析BMI与各激素的相互关系. [结果]①肥胖组儿童BMI及血清Leptin、Ins、IGF-Ⅰ、IGF-BP3和E2水平明显高于正常组,且差异有显著性(P值均<0.001),而两组睾酮水平差异无显著性(P>0.05);相关分析显示肥胖儿童BMI与血清Leptin和Ins水平有明显正相关(r=0.412,r=0.336.P值均<0.001);②正常组儿童BMI与血清Leptin、Ins、IGF-Ⅰ、IGF-BP3、E2和睾酮水平均无相关性(P值均>0.05),③BMI与血清Leptin和Ins水平的相关系数肥胖男童大于肥胖女童,且肥胖女童BMI与血清E2水平有显著正相关(P<0.05),而肥胖男童则无显著相关性(P>0.05);④多元线性回归分析显示肥胖儿童血清Leptin和Ins水平是影响BMI的重要因素(P值均<0.001). [结论]BMI对儿童肥胖的早期诊断、早期干预是非常有意义的.     

学龄前单纯性肥胖儿童血清瘦素、胰岛素及性激素水平

目的:探讨学龄前单纯性肥胖儿童血清瘦素(Leptin)、胰岛素(Ins)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)、胰岛素样生长因子结合蛋白-3(IGF-BP3)、雌二醇(E2)和睾酮(T)水平,为单纯性肥胖儿童的早期干预提供理论依据。方法:对122例学龄前单纯性肥胖儿童及61例正常儿童血清Leptin、Ins、IGF-Ⅰ、IGF-BP3、E2和T水平进行测定。结果:学龄前单纯性肥胖儿童血清Leptin、Ins、IGF-Ⅰ、IGF-BP3和E2水平明显高于正常对照组(P均0.001),两组间睾酮水平差异无统计学意义(P0.05);肥胖女童血清E2水平明显高于肥胖男童(P0.01),但Leptin、Ins、IGF-Ⅰ、IGF-BP3和睾酮水平肥胖男女童之间差异无统计学意义(P均0.05);大年龄组(5～6岁)肥胖儿童血清Leptin、Ins、IGF-Ⅰ、IGF-BP3、E2和睾酮水平明显高于小年龄组(2～4岁)肥胖儿童(P均0.05)。结论:学龄前单纯性肥胖儿童存在高瘦素血症、高胰岛素血症和肥胖女童的高雌激素血症,是肥胖儿童未来糖尿病、心血管疾病、性早熟等危险因素。     

单纯性肥胖儿童血清Leptin、IGF1、IGFBP3及性激素变化

目的探讨单纯性肥胖儿童血清瘦素(Leptin)、胰岛素样生长因子-1(IGF1)、胰岛素样生长因子结合蛋白-3(IGFBP3)、雌二醇(E2)及睾酮(T)水平及其相互关系.方法用放免法检测61例青春期前肥胖儿童和60例健康儿童的血清Leptin、IGF1、IGFBP3水平,采用全自动荧光免疫分析仪测定E2及T.结果肥胖儿童血清Leptin、IGF1及E2水平均显著高于健康对照组(P均＜0.01), 肥胖女童IGFBP3高于对照组(P＜0.05),而肥胖男童T水平则明显低于对照组(P＜0.01).结论单纯性肥胖儿童存在瘦素抵抗及内分泌代谢紊乱,瘦素抵抗可能在肥胖的发生发展中起重要作用.     

单纯性肥胖女孩3种激素水平及与BMI的关系

目的探讨不同年龄段单纯性肥胖女孩的血清瘦素(Leptin)、雌二醇(E2)、胰岛素(Ins)3种激素水平和内分泌相互作用及与体重指数(BMI)之间的关系,以便为青春期女生生长发育的研究提供依据.方法对荥阳市6所中小学女生2 000名测量体重后,从筛查出的单纯性肥胖儿童中随机抽取60名,同时从正常体重女生中抽取60名为对照.按年龄分组,分别用放射免疫方法(RIA)测定其血清3种激素的含量.结果各年龄组对照组和肥胖组女孩的Leptin和Ins水平差异有显著性(P＜0.05),各年龄组Leptin和Ins水平与BMI有明显的相关性(P＜0.05).结论 3种激素水平均随年龄、体重和BMI的升高而升高.肥胖女孩的Leptin和Ins分泌紊乱.瘦素水平能从一定程度上反应肥胖的程度,结合内分泌水平可对肥胖程度以准确评价.     

单纯性肥胖男童血清瘦素与胰岛素性激素检测结果 分析

目的 研究单纯性肥胖男性儿童血清瘦素、胰岛素及性激素水平之间的关系,为青少年肥胖的干预提供依据.方法 以10～15岁单纯性肥胖和正常对照儿童各22名为研究对象,用放射免疫法测定血清中的瘦素、胰岛素和性激素水平.结果 单纯性肥胖男生血清瘦素、胰岛素和雌二醇水平显著高于正常男童(P值均＜0.01),睾酮水平则明显低于正常男童(P＜0.01).血清瘦素水平与胰岛素、睾酮、雌二醇水平均有显著相关(P值均＜0.01).结论 高水平瘦素可能是单纯性肥胖重要的生物学标志之一.单纯性肥胖男童存在性激素代谢紊乱、性发育落后,瘦素可能影响男性肥胖儿童的性发育.     

单纯性肥胖儿童血中瘦素水平及其调控因子研究

目的　研究单纯性肥胖儿童血中瘦素水平及其调控因子。方法　检测 42对 1 0～ 1 2岁肥胖儿童血中瘦素 (Leptin)及其调控因子胰岛素 (Ins)、神经肽Y(NPY)和肿瘤坏死因子α(TNFα)。结果　肥胖儿童血中Lepin含量 [(9.33± 2 .1 4 )ng ml]非常显著地高于对照组含量 [(3 .47± 2 .57)ng ml] (P <0 .0 1 ) ,肥胖组Ins[(2 4 .75± 1 2 .75)mIu L]亦高于对照组 [(1 9.1 9± 6 .39)mIu L] (P <0 .0 5) ,肥胖组TNFα[(1 2 .62± 4 .50 )ng ml]非常显著地低于对照组 [(1 4 .43± 5 .56)ng ml] (P <0 .0 1 ) ,NPY两组间差异无显著性。女性血中Leptin水平 [(1 0 .0 0± 1 .1 2 )ng ml]显著高于男生 [(3 .72± 1 .1 1 )ng ml] (P <0 .0 1 ) ,重度肥胖组Leptin水平 (1 6 .59ng ml)高于轻度肥胖组 (7.91ng ml) (P <0 .0 5)。结论　肥胖儿童血中Leptin含量升高 ;肥胖者体内Ins含量增加 ,NPY和TNFα产生减少与Leptin的调控有关     

人胰岛素生长因子BP3、makorin环指蛋白3在特发性中枢性性早熟女童诊断中的应用价值

目的检测特发性中枢性性早熟(ICPP)女童血清中人胰岛素生长因子BP3(IGF-BP3)、makorin环指蛋白3(MKRN3)水平,并探讨IGF-BP3、MKRN3在ICPP女童诊断中的应用价值。方法选取2017年3月-2019年3月于本院就诊的95例ICPP女童(ICPP组)为研究对象,同期选取83例健康体检女童(CG组)作为对照组。采用化学发光法检测2组激素水平;全自动免疫分析仪检测血清中IGF-BP3水平、qRT-PCR法检测血清中MKRN3水平;分析IGF-BP3、MKRN3水平与一般资料、激素水平的相关性;分析IGF-BP3、MKRN3对ICPP女童的诊断价值。结果 ICPP组IGF-BP3水平、骨龄、泌乳素(PRL)、雌二醇(E2)显著高于CG组(P <0.05),MKRN3、乳房发育年龄水平显著低于CG组(P <0.05);骨龄、PRL、E2与IGF-BP3水平均呈正相关,与MKRN3水平均呈负相关(P <0.05);乳房发育年龄与IGF-BP3水平呈负相关,与MKRN3水平呈正相关(P <0.05);IGF-BP3、E2是ICPP疾病发生的危险因素,MKRN3是ICPP疾病发生的保护因素;IGF-BP3、MKRN3联合诊断ICPP疾病的AUC为0.918(95%CI:0.875~0.961),特异度为87.4%,敏感度为86.7%。结论 IGF-BP3、MKRN3在ICPP发生中发挥重要作用,可能参与ICPP发病机制,IGF-BP3联合MKRN3可作为诊断ICPP女童的参考指标。     

多囊卵巢综合征IGF-Ⅰ、IGFBP-1影响因素探讨

[目的]探讨多囊卵巢综合征(PCOS)患者胰岛索生长因子-Ⅰ(IGF-Ⅰ)、胰岛素生长因子结合球蛋白-1(IGFBP-1)水平与促卵泡素(LH)、肥胖、胰岛素抵抗或高雄激素血症的关系.[方法]免疫放射法分析31例PCOS研究组和29例对照组IGF-Ⅰ、IGFBP-1水平,比较两组间差异;再将研究组以有无LH增高、肥胖、胰岛素抵抗及高雄激素血症为标准各分为两组,比较每两组间IGF-I、IGFBP-1的差异.[结果]研究组与对照组比较,IGF-Ⅰ显著下降(P＜0.01),IGFBP-1显著升高(P＜0.01).研究组肥胖者与非肥胖者IGFBP-Ⅰ比较差异有统计学意义(P＜0.01),IGF-Ⅰ比较差异无统计学意义(P＞0.05).LH增高者与LH正常者、胰岛素抵抗与胰岛素正常者、高雄激素血症与雄激素正常者比较,IGF-Ⅰ、IGFBP-1均差异无统计学意义(P＞ 0.05).IGFBP-1与BMI呈负相关(r=-0.372).[结论]IGF-BP-1与 PCOS患者肥胖密切相关.     

多囊卵巢综合征IGF-I、IGFBP-1影响因素探讨

[目的]探讨多囊卵巢综合征(PCOS)患者胰岛素生长因子-I(IGF-I)、胰岛素生长因子结合球蛋白-1(IGFBP-1)水平与促卵泡素(LH)、肥胖、胰岛素抵抗或高雄激素血症的关系。[方法]免疫放射法分析31例PCOS研究组和29例对照组IGF-I、IGFBP-1水平,比较两组间差异;再将研究组以有无LH增高、肥胖、胰岛素抵抗及高雄激素血症为标准各分为两组,比较每两组间IGF-I、IGFBP-1的差异。[结果]研究组与对照组比较,IGF-I显著下降(P﹤0.01),IGFBP-1显著升高(P﹤0.01)。研究组肥胖者与非肥胖者IGFBP-I比较差异有统计学意义(P﹤0.01),IGF-I比较差异无统计学意义(P﹥0.05)。LH增高者与LH正常者、胰岛素抵抗与胰岛素正常者、高雄激素血症与雄激素正常者比较,IGF-I、IGFBP-1均差异无统计学意义(P﹥0.05)。IGFBP-1与BMI呈负相关(r=-0.372)。[结论]IGF-BP-1与PCOS患者肥胖密切相关。     

Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women

BACKGROUND: Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol's effects on IGF-I or IGFBP-3 have not been conducted. OBJECTIVE: To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. DESIGN: Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjusted to maintain constant weight, and serum was collected at the end of each diet period. RESULTS: Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: -3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: -8.0%, -1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: -0.9%, 4.5%). CONCLUSIONS: To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findings suggest that the effect of alcohol intake should be considered in studies of IGF-I, IGFBP-3, and cancer in postmenopausal women.     

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。     

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.     

Protein nutrition and insulin-like growth factor system

Protein metabolism of growing animals is greatly affected by quantity and nutritional quality of dietary proteins. When animals are fed diets that contain enough proteins of good nutritional quality, they grow well. However, if they are fed diets deficient in protein or in some essential amino acids, their growth rate is markedly depressed. In this paper, we review the response of plasma insulin-like growth factor-I (IGF-I) to quantity and nutritional quality of dietary proteins. The sound correlation between plasma IGF-I concentration and the gain or loss of body proteins under various nutritional conditions suggests that the plasma IGF-I most possibly regulates the growth rate of animals or the rate of whole body protein synthesis. The quantity and nutritional quality of dietary proteins also regulates plasma concentration of IGF-binding proteins (IGFBPs). The changes in plasma concentration of IGFBPs presumably modifies the activity of IGF-I to regulate whole body protein synthesis. Molecular mechanisms of the changes in plasma concentrations of IGF-I and IGFBPs as affected by dietary proteins are also reviewed.     

Enterotrophic effect of insulin-like growth factor-I but not growth hormone and localized expression of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and -5 mRNAs in jejunum of parenterally fed rats

BACKGROUND: Administration of insulin-like growth factor (IGF)-I, but not growth hormone (GH), stimulates mucosal hyperplasia in surgically stressed rats with intestinal atrophy induced by hypocaloric total parenteral nutrition (TPN). Our aim was to characterize the basis for this disparity in enterotrophic action by assessing the relationships between stimulation of intestinal growth, nutritional adequacy, and localization of expression of IGF-I, insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5 mRNAs in jejunum. METHODS: Rats were maintained with TPN for 8 days and treated with IGF-I or GH and adequate nutrition for 5 days after recovery from surgery. Jejunal mass, morphology, and sucrase activity were assessed. Localization of expression of IGF-I, IGFBP-3, and IGFBP-5 mRNAs in jejunum was accomplished by in situ hybridization. RESULTS: Serum IGF-I and body weight gain were significantly increased by IGF-I or GH. Jejunal mucosal dry mass, morphology, and sucrase activity were improved with IGF-I but not GH. There were no differences in IGF-I mRNA. IGFBP-3 mRNA was localized in the lamina propria of the villi. IGF-I or GH stimulated IGFBP-3 expression. IGF-I strongly stimulated IGFBP-5 expression in the lamina propria and the muscularis and induced a twofold increase in IGFBP-5 mRNA based on RNase protection assay of intact jejunum total RNA. GH induced a modest increase in IGFBP-5 expression in the muscularis with no effect on intact jejunum total RNA. CONCLUSIONS: The GH resistance observed in the jejunal mucosa of TPN rats cannot be fully explained by inadequate nutrition. The expression of IGFBP-5 in the lamina propria suggests it may modulate the enterotrophic action of exogeneous IGF-I.     

Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection

The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.     

Anthropometric and behavioral correlates of insulin-like growth factor I and insulin-like growth factor binding protein 3 in middle-aged Japanese men

High levels of plasma insulin-like growth factor I (IGF-I) and low levels of insulin-like growth factor binding protein 3 (IGFBP-3) have been related to increased risk of several cancers. Little is known about the behavioral determinants of these biologic markers. The authors examined the relation of anthropometric and behavioral factors to plasma concentrations of IGF-I and IGFBP-3 in a cross-sectional study of 616 Japanese men aged 45-55 years in 1995-1996. In univariate analyses, body mass index was strongly, positively associated with both IGF-I and IGFBP-3. The waist/hip ratio was also linearly related to IGF-I and IGFBP-3 up to the third quartile level. Height was weakly, positively associated with IGF-I and IGFBP-3. Smoking was inversely associated with IGF-I and IGFBP-3. Alcohol use was associated inversely with IGF-I and positively with IGFBP-3. Neither IGF-I nor IGFBP-3 was related to physical activity. Results of the multivariate analysis were essentially the same as those of the univariate analyses. The findings regarding body mass index are in contrast to those of previous studies showing null or inverse associations, and they suggest that the relation of body mass index to IGF-I or IGFBP-3 may vary among populations. The study also indicates that smoking and alcohol use might affect plasma IGF-I and IGFBP-3.     

Development of the insulin-like growth factor-I assay system

A high speed full automatic ELISA system for measurement of insulin-like growth factor-I (IGF-I) was established by using magnetic particle-linked monoclonal antibody and enzyme-labeled monoclonal antibody. A standard curve was obtained, and the effect of dilution on the assay system was investigated. An IGF-I spike recovery test of human serum samples and a study of the correlation with a radioimmunoassay system were performed, and good results were obtained from all studies. The assay range was 0.5-50 ng/ml, and the time required for the full automatic measurement was 15 minutes. This assay system will play a central role in the clinical approach to IGF-I.     

Body size in early life and adult levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3

Body size in early life has been associated with breast cancer risk. This may be partly mediated through the insulin-like growth factor (IGF) pathway. The authors assessed whether birth weight, body fatness at ages 5 and 10 years, and body mass index (BMI; weight (kg)/height (m)(2)) at age 18 years were associated with plasma concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 in 6,520 women aged 32-70 years at blood draw from the Nurses' Health Study (1990-2006) and Nurses' Health Study II (1997-2005). Birth weight, body fatness in childhood, and BMI at age 18 years were inversely associated with adult IGF-1 levels. For example, IGF-1 levels were 11.9% lower in women who reported being heaviest at age 10 years than in those who were leanest at age 10 (P-trend < 0.0001). Further, women who reported their birth weight as ≥10 pounds (≥4.5 kg) (vs. <5.5 pounds (<2.5 kg)) had 7.9% lower IGF-1 levels (P-trend = 0.002). Women whose BMI at age 18 years was ≥30 (vs. <20) had 14.1% lower IGF-1 levels (P-trend < 0.0001). Similar inverse associations were observed for insulin-like growth factor binding protein 3. These observations did not vary by adult BMI or menopausal status at blood draw. These findings suggest that altered IGF-1 levels in adulthood may be a mechanism through which early-life body size influences subsequent breast cancer risk.