不同运动方式对大鼠肝脏胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3及瘦素受体的影响

目的探讨不同运动方式对大鼠肝脏胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)和瘦素受体含量的影响。方法 24只大鼠随机分为安静组(C组)、耐力训练组(E组)、高强度间歇性训练组(S组)和悬吊组(D组)4组,每组6只,训练8周;采用Bed-ford训练方案,耐力训练相当于65%VO2max;末次训练后24h各组大鼠安静状态下处死,取肝脏。采用酶联免疫吸附测试(定量)法分别测定肝脏中IGF-1、IGFBP-3和瘦素受体含量。结果 E组IGF-1蛋白含量显著高于C组(P0.05);S组IGFBP-3蛋白含量极显著高于C组(P0.01);S组IG-FBP-3/IGF-1比值显著高于E组(P0.05);E组、S组瘦素受体含量显著高于C组(P0.05)。结论运动诱导的IGF-1、IGFBP-3和瘦素受体含量变化具有运动方式以及运动强度的敏感性,寻求IGF-1和IGFBP-3之间恰当的比值对于促进人类健康将会有非常重要的意义。     

血清IGF—1、IGFBP—1，GH水平与糖尿病慢性并发症关系的研究

目的：揭示胰岛素样生长因子－1,胰岛素样生长因子结合蛋白－1,生长激素对糖尿病慢性并发症的发生,发展的影响。方法：测定20例健康对照者和62例2例糖尿病,10例1例糖尿病患者的胰岛素样生长因子－1（IGF－1）,胰岛素样生长因子结合蛋白－1（IGFBP－1）,生长激素（GH）及血浆胰岛素（INS）,C肽（C－P）,糖化血红蛋白（HbAlc)指标,结果：（1）IGF－1水平,1型糖尿病患者显著低于对照组（P＜0．05）,2型糖尿病患者显著低于对照组（P＜0．05）,（2）IGFBP－1水平,1型糖尿病患者显著高于对照组（P＜0．05）,2型糖尿病肥胖型伴高胰岛素血症者显著低于对照组（P＜0．05）;（3）GH水平,1型糖尿病患者显著高于对照组（P＜0．05）,2型糖尿病与对照组无显著差异（P＞0．05）,（4）合并糖尿病肾病及视网膜病变患者IGF－1水平均较对照组增高（P＜0．05）,（5）IGF－1水平与HbAlc间呈负相关（P＜0．01 2型r=-0.62 1型r=-0.73)。结 论：IGF－1,IGFBP－1,GH水平的检测对糖尿病慢性并发症,特别是微血管病变的发生,发展有重要的临床意义。     

血清胰岛素样生长因子及其结合蛋白诊断儿童生长激素缺乏症的价值

为了解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）浓度与生长激素缺乏症（GHD）患儿生长激素（GH）激发试验中血清生长激素峰值的关系,以确定血清IGF－1,IGFBP－3浓度诊断GHD的价值,为其代替GH激发试验提供依据,选择GHD患儿62例（男39例,女23例）为GHD组,60例健康儿童（男38例,女22例）为对照组。分别用放射免疫分析（RIA）法,免疫放射分析（IRMA）法检测GHD组血清IGF－1,IGFBP－3浓度,同时被GH激发试验,测定血清GH峰值,并比较其与IGF－1,IGFBP－3的关系,测定对照组血清IGF－1,IGFBP－3。结果显示,GHD组血清IGF－1,IGFBP－3均显著低于对照组（t分别为3.116,11.579,p均＜0．01）;GHD组血清IGF－1,IGFBP－3浓度与GH激发试验中的GH峰值呈显著正相关（r分别为。331,0。347,P均＜0．01）;GHD组血清IGF－1,IGFBP－3降低的阳笥率分别为97．58％,98．38％,与激发试验的阳性率（100％）,比较无统计学意义（x^2分别为.3074,2.033,P均＞0．05）。表明血清中IGF－1,IGFBP－3浓度检测对诊断GHD有重要价值,认为检测血清中IGF－1,IGFBP－3浓度可以替代GH激发试验。     

Effects of dynamic exercise on circulating IGF-1 and IGFBP-3 levels in patients with rheumatoid arthritis or ankylosing spondylitis

This study was performed to determine the effects of short-term dynamic exercise on serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in the patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Patients with RA or AS and healthy controls were recruited. Dynamic treadmill exercise therapy was accomplished for 20 min/session with all of the participants. There were five sessions per week for 2 weeks. Morning stiffness duration, body pain, Stanford health assessment questionnaire, Ritchie articular index, Bath ankylosing spondylitis disease activity index (BASDAI), and Bath ankylosing spondylitis functional index (BASFI) were evaluated in the RA and AS patients. Laboratory assessments included: erythrocyte sedimentation rate, serum C-reactive protein, IGF-1, and IGFBP-3. Clinical and laboratory assessments were recorded at baseline and during exercise treatment on days 7 and 15. Twenty patients with RA, 15 with AS, and 14 healthy controls were included in this study. The pain evaluation, Ritchie, BASDAI, and BASFI scores were significantly improved by the exercise treatment in both patient groups. The important increases were found in circulating IGF-1 in RA (p < 0.001) and AS (p = 0.001) at the end of 2 weeks. In control individuals, serum IGF-1 levels showed a significant decline in the first week (p < 0.05). No significant changes were observed on serum IGFBP-3 levels. Our data suggest that serum IGF-1 levels are increased by the dynamic exercise program in RA and AS patients. The increased IGF-1 may play an important role in the beneficial effects of dynamic exercise therapy in these patients.     

Common polymorphisms in the GH/IGF-1 axis contribute to growth in extremely tall subjects

Context/objective

The growth hormone (GH)/insulin-like growth factor-1(IGF-1) axis is the key regulator of somatic growth in humans and its genes are plausible candidates to study the genetics of height variation. Here, we studied polymorphic variation in the GH/IGF-1 axis in the extremely tall Dutch.

Methods

Case–control study of 166 tall cases with height > 2 SDS and 206 controls with normally distributed height < 2 SDS. Excluded were subjects with endocrine disorders or growth syndromes. We analyzed genomic DNA at 7 common polymorphisms in the GH-1, GH receptor (GHR), IGF-1 and IGFBP-3 genes.

Results

The association of the GH-1 1663 SNP with tall stature approached statistical significance, with the T-allele more present in the tall (allele frequency (AF): 0.44 vs. 0.36; p = 0.084). Moreover, haplotype frequencies at this locus were significantly different between cases and controls, with the GGT haplotype most commonly seen in cases (p = 0.01). Allele frequencies of GHR polymorphisms were not different. For the IGF-1 CA-repeat we observed a higher frequency of homozygous 192-bp carriers among tall males compared to control males (AF: 0.62 vs. 0.55; p = 0.02). The IGFBP-3 -202 C-allele occurred more frequently in cases than in controls (AF: 0.58 vs. 0.50; p = 0.002). Within cases, those carrying one or two copies of the -202 C-allele were significantly taller than AA genotype carriers (AC, p = 0.028 and CC, p = 0.009). Serum IGFBP-3 levels were highest in AA genotype carriers, the -202 SNP explained 5.8% of the variation.

Conclusion

Polymorphic variation in the GH-1, IGF-1 and IGFBP-3 genes is associated with extremely tall stature. In particular, the IGFBP-3 -202 SNP is associated not only with being very tall but also with height variation within the tall.     

耐力运动对高脂膳食大鼠肝脏瘦素受体、IGF-1及IGFBP-3的影响

目的 探讨耐力运动对高脂膳食大鼠肝脏胰岛素样生长因子1 (IGF-1)、胰岛素样生长因子结合蛋白3 (IGFBP-3) 和瘦素受体含量的影响.方法 20只大鼠随机分为安静组(H组)和耐力训练组(R组),每组10只,训练8 w;采用Bedford训练方案,耐力训练相当于65%VO2max;末次训练后24 h各组大鼠安静状态下处死,取肝脏.采用酶联免疫吸附测试 (定量) 法分别测定肝脏中IGF-1、IGFBP-3和瘦素受体含量.结果 R组IGF-1蛋白含量显著高于H组(P<0.05);R组IGFBP-3蛋白含量显著高于H组(P<0.05);两组IGFBP-3/IGF-1比值没有显著性差异;R组瘦素受体含量非常显著高于H组(P<0.01).结论 耐力运动能够促进高脂膳食大鼠IGF-1、IGFBP-3和瘦素受体的表达,是一种十分有效的治疗方式,对于促进机体健康有一定意义.     

The serum levels of proinsulin and their relationship with IGFBP-1 in obese children

AIM: Serum proinsulin (PI) levels were investigated in obese children to determine whether PI is a sensitive indicator of insulin resistance, as previously shown in adults with type 2 diabetes mellitus (DM), and to evaluate their relationship with insulin-like growth factor-binding protein-1 (IGFBP-1) known as a predictor of the development of cardiovascular disease in diabetic adults. SUBJECTS AND METHODS: Forty-two obese children without DM (age, 12.1 +/- 1.5 year) and 42 age-matched control children were included in the study. The serum levels of PI, immunoreactive insulin (IRI), IGFBP-1 and free insulin-like growth factor-1 (IGF-1) were measured in the fasting state. RESULTS: The fasting levels of serum PI and IRI were significantly higher in obese children than in controls (PI, 10.5 +/- 6.8 vs. 5.6 +/- 2.0 pmol/l, p < 0.001; IRI, 72.0 +/- 41.8 vs. 32.7 +/- 19.5 pmol/l, p < 0.001). Serum IGFBP-1 levels were significantly lower in obese children than in controls (37.7 +/- 24.6 vs. 76.3 +/- 26.5 microg/l, p < 0.001). The ratio of PI to IRI (calculated as molar ratios) did not differ significantly between obese and control subjects (0.16 +/- 0.08 vs. 0.19 +/- 0.11, p = 0.08). For the whole group, serum PI levels correlated positively with IRI and inversely with IGFBP-1 (IRI, r = 0.67, p < 0.001; IGFBP-1, r = -0.49, p < 0.001). Serum IGFBP-1 levels correlated inversely with both BMI and IRI (BMI, r = -0.73, p < 0.001; IRI, r = -0.60, p < 0.001). Multiple regression analysis revealed that the best predictive parameters for IGFBP-1 were BMI and PI (R2 = 0.57, p < 0.001 and p < 0.05, respectively). CONCLUSION: These findings suggest that fasting serum PI levels may be a better predictor than fasting insulin levels for the future development of type 2 DM and cardiovascular disease in obese children, and PI, in addition to insulin, contributes to the suppression of hepatic IGFBP-1 production.     

Changes in total ghrelin within the somatotropic axis in severe burn patients: Comparison of those with inhalation injury and those without inhalation injury

OBJECTIVE: The aims of this study were to clarify changes in total ghrelin within the somatotropic axis in severe burn subjects with or without inhalation injury as well as the responsiveness of GH, IGF-1, and IGFBP-3 to the different severity of burn injuries. DESIGN: Twenty-three patients with severe burn injuries (>30% of 2nd degree burns or >10% of 3rd degree burns) were classified into 2 groups according to inhalation injury: group I with inhalation injury (n=9) and group II without inhalation injury (n=14). The evaluations of serum GH, IGF-1, IGFBP-3, and total ghrelin were done on post-burn injury days 3, 7, 14, 21, and 40. Cortisol levels were measured from 24-h urine collections on post-burn injury days 7 and 21. RESULTS: In all subjects, the levels of GH fluctuated throughout the observation period whereas IGF-1 showed an initial decline with nadir on day 7 and a subsequent increase through day 40. The levels of IGFBP-3 and total ghrelin showed a progressive increase with nadir on day 3. Compared with the group II, the GH levels were increased in the group I on post-burn days 3, 7, and 14, of which day 7 showed statistical significance (p<0.05). The levels of IGF-1 (days 7 and 21; p<0.05) and IGFBP-3 (days 7, 14, 21, and 40; p<0.05, p<0.01, p<0.05, p<0.05, respectively) were lower in the group I than in the group II throughout the study period. On post-burn injury days 3, 7, 14, and 21, total ghrelin levels were lower in the group I than in the group II with statistical significance on post-burn day 7 (p<0.001). CONCLUSIONS: Our present data show a concurrence of elevated GH levels and decreased IGF-I, IGFBP-3, and total ghrelin levels during the early burn injury period, in addition to more GH burst amplitude as well as greater falling of IGF-I, IGFBP-3 and total ghrelin levels proportional to the severity of burn injury. Further studies are needed to ascertain whether acyl- and desacyl-ghrelin instead of total ghrelin are completely independent of increased GH or other stress mediators, and whether GH-releasing hormone (GHRH) mainly stimulates the production and release of GH in acute critical conditions.     

生长激素/胰岛素样生长因子-1与免疫系统的关系

生长激素(GH)及胰岛素样生长因子(IGF)-1与免疫系统具有相互调节作用。GH可恢复胸腺形态、结构,促进胸腺细胞的分化、成熟,并可激发免疫系统原始细胞的迁移、分化、成熟,提高中性粒细胞、淋巴细胞、巨噬细胞的作用。免疫系统主要通过炎症因子白细胞介素-6及肿瘤坏死因子-α的作用影响GH/IGF-1,减少其水平,降低其活性,削弱GH治疗的效应,导致GH抵抗。     

Assessment of age-related changes in heritability and IGF-1 gene effect on circulating IGF-1 levels

It is well established that insulin-like growth factor 1 (IGF-1) circulating levels correlate with age and that heritability and influence of IGF-1 gene variation on IGF-1 levels also well-known. However, the influence of age on the genetic factors determining IGF-1 levels is not clear. In this study, we compared heritability estimates between younger (<52 years) and older (>52 years) twins and tested: (a) whether single nucleotide polymorphisms (SNPs) lying within 100 kbp of the IGF-1 gene are also associated with IGF-1 variation and (b) whether associated SNPs show interaction with age on IGF-1 levels. To achieve these aims, we measured plasma levels of IGF-1 and genotyped 18 SNPs with minor allele frequency >0.1 in a large sample, 4,471 UK female twins. Heritability explained 42 % of IGF-1 variation adjusted for age and in unadjusted sample was independent of age. Ten SNPs in four haploblocks showed significant association with IGF-1 levels, with p = 0.01–0.0005. The most distal SNP was located up to 90 kbp from the IGF-1 gene. When their age-dependent effects were examined, one SNP, rs855203, showed significant (p = 0.0009) age-dependent interaction effect on IGF-1 levels variation. This is the first study to test the age × genotype interaction in IGF-1 levels. The genomic region marked by rs855203 may consequently be of significance for further molecular and pharmacogenetic research, in particular in advanced age.     

胃癌及其区域淋巴结中PTEN、IGF-1/IGF-1R mRNA的表达

目的探讨胃癌及其区域淋巴结中MMAC1基因（PTEN）,胰岛素样生长因子1（IGF-1）/胰岛素样生长因子1受体（IGF-1R）mRNA的表达及其在胃癌发生和淋巴结转移中的作用。方法RT-PCR方法检测胃癌组织、正常胃黏膜、胃癌区域淋巴结中PTEN,IGF-1/IGF-1R mRNA的表达。结果胃癌组织中PTEN mRNA表达降低,IGF-1/IGF-1R mRNA表达增高,PTEN/IGF的表达与年龄,性别无关,与肿瘤的分期、分化程度及淋巴结转移明显相关。转移淋巴结中PTEN/IGF表达失衡,并且比原发灶中的失衡更加严重。结论PTEN mRNA表达降低,IGF-1/IGF-1R mRNA表达增高对胃癌的发生和转移起着重要作用。     

胰岛素样生长因子-1与胰岛素敏感性的关系

目的探讨胰岛素样生长因子1(IGF1)与胰岛素敏感性(IS)的关系。方法40例非糖尿病患者和68例新诊断的2型糖尿病患者参加研究,收集这些受试者的一般资料和生化特征资料。结果IGF1浓度与年龄、体重指数(BMI)、甘油三酯(TG)水平和收缩压及舒张压成负相关。IGF1浓度与高密度脂蛋白胆固醇(HDLC)和胰岛素敏感性的稳态评估(HOMAIR)成正相关。在包括性别、年龄、BMI、收缩压和舒张压、HDLC和甘油三酯等胰岛素敏感性调节因子在内的逐步线性回归分析发现,IGF1浓度独立的与胰岛素敏感性相关。符合世界卫生组织(WHO)定义的代谢综合征个体与非代谢综合征个体相比,IGF1浓度明显降低(P<0.01)。结论IGF1具有作为胰岛素抵抗综合征标志物的特征。较低的IGF1水平可能是一个确定具有心血管疾病风险个体的有用的标志物。     

Low hemoglobin levels in children with in idiopathic growth hormone deficiency

Multiple lines of evidence have implicated the growth hormone (GH) axis in the regulation of erythropoiesis. To test the hypothesis that GH deficiency is associated with hematologic abnormalities, we analyzed pretreatment hemoglobin levels in 100 children with GH deficiency. Hemoglobin levels were decreased in children with GH deficiency compared with age-corrected norms.     

Current Practice in Diagnosis and Treatment of Growth Hormone Deficiency in Childhood: A Survey from Turkey

Objective:

Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey.

Methods:

A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers.

Results:

Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height.

Conclusion:

Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.     

Insulinlike Growth Factor-1, Insulinlike Growth Factor Binding Protein-1, and Cognitive Function in Older Men and Women

OBJECTIVES: To assess the association between insulinlike growth factor (IGF)-1 and IGF binding protein (IGFBP)-1 with three cognitive function tests in a healthy elderly population.
DESIGN: Cross-sectional analyses from the Rancho Bernardo Cohort Study.
SETTING: Southern California community of Rancho Bernardo.
PARTICIPANTS: Men (n=636) and women (n=899) from the Rancho Bernardo study (median age 74) were assessed between 1988 and 1992 for cognitive function using the Mini-Mental State Examination (MMSE), Verbal Fluency (VF) test, and Trail-Making Test Part B (Trails B). Blood samples were obtained at the same time for IGF-1 and IGFBP-1 levels. The association between biomarkers and cognitive function tests was assessed by dichotomizing tests at the clinically relevant cutoff using logistic regression and according to tertiles and continuous IGF-1 and IGFBP-1 levels using multivariate linear regression analyses.
RESULTS: The mean MMSE, VF and Trails B scores indicated better cognitive function with higher IGF-1 tertile. Multivariate analyses showed that VF and MMSE were each significantly associated with IGF-1 in a dose-response manner for men ( P for trend=.001), but no cognitive function tests were related to IGF-1 in women. For men, the highest IGFBP-1 tertile was inversely and significantly different from the lowest tertile for the MMSE test only ( P for trend=.02).
CONCLUSION: IGF-1 was independently and positively related to MMSE and VF in men, and IGFBP-1 was inversely associated with MMSE in men. Sex differences in the association should be further investigated.     

IGF-1对Rh1肉瘤细胞PI3K/Akt/mTOR信号通路的影响

目的 探讨胰岛素样生长因子(IGF)1对Rh1肉瘤细胞生长活性和PI3 K/Akt/mTOR信号通路的背景变化.方法 常规细胞培养,用无血清培养基消除内源性因子影响27h,再用IGF-1(终浓度为10 ng/ml)刺激72 h,流式细胞仪检测细胞生长活性;另外Western印迹方法观察IGF-1刺激细胞5、10、20、30和60min后Akt(s473)、S6的动态变化.结果 与对照组相比,IGF-1可促进Rh1细胞存活.IGF-1刺激不同时间后S6磷酸化则随着时间的延长逐渐增强;IGF-1亦导致Akt(s473)位点的磷酸化,随时间的延长,磷酸化Akt在5min时达高峰,此后逐渐减弱.结论 Akt、S6等是PI3K/Akt/mTOR信号通路中的重要信号分子,对Rhl细胞而言,在IGF-1刺激下S6有逐渐增强的变化,Akt (s473)位点磷酸化则有减弱的动态变化.     

IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI

OBJECTIVE: Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely. STUDY DESIGN: Fifty subjects, all women, were evaluated at a mean age +/- SD of 26 +/- 2 years (range: 23-30 years). They were allocated to three groups: (i) born fullterm with birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with appropriate birth weight (n = 17). Anthropometric data as well as fasting serum samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were determined. RESULTS: In the SGA group final height was lower and they weighed less compared with the controls. Fasting insulin and glucose levels did not differ amongst the groups. Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls (P < 0.05). The SGA group showed lower IGFBP-1 levels compared with the controls median 17 (range 3-121) vs. 26 (7-67) microg L-1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control groups were 212 +/- 58, 259 +/- 37 and 216 +/- 32 microg L-1, respectively, corresponding to a mean SD score of -0.8 +/- 1.0, 0.1 +/- 0.6 and -0.6 +/- 0.6. CONCLUSION: As IGFBP-1 is a marker of insulin sensitivity, the low levels observed in adult women with normal BMI, born small for date, suggest relative insulin resistance in spite of normal BMI.