Insulin-like growth factor binding protein-1 levels in diabetic adolescents and their relationship to metabolic control.

Circulating levels of the low molecular weight insulin-like growth factor binding protein-1 (IGFBP-1) are insulin dependent and vary markedly throughout the day. IGFBP-1 levels are abnormally high in diabetes but the relationship between this and the metabolic status of the patient has not been defined. We have therefore measured fasting IGFBP-1 levels at 0800 h in 32 diabetic adolescents. IGFBP-1 was measured in 19 of these patients after a normal night and in 27 after a night of euglycaemia, maintained with a glucose clamp. In 13 patients both studies were performed and could be compared. Puberty-matched control data were obtained from 69 normal children. In normal prepubertal children IGFBP-1 levels were high; lower levels were found with advancing pubertal development. This fall in IGFBP-1 correlated with pubertal stage (r= 0.68, p less than 0.001) and with fasting insulin levels (r = 0.60, p less than 0.001) which rose with pubertal advancement. In the diabetic children IGFBP-1 levels also correlated inversely with the 0800 h free insulin level but there was no clear relationship with pubertal development. However, when measured after overnight euglycaemia IGFBP-1 levels correlated inversely with pubertal development (r = 0.67, p less than 0.001) as in the normal children. In the patients studied on two comparable occasions the IGFBP-1 level measured after a normal night relative to that measured under standardized euglycaemic conditions was found to correlate closely with the glycosylated haemoglobin level (r = 0.71, p less than 0.005).     

Effects of swimming training on bone mass and the GH/IGF-1 axis in diabetic rats

The aim of this study was to examine the influence of moderate swimming training on the GH/IGF-1 growth axis and tibial mass in diabetic rats. Male Wistar rats were allocated to one of four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced with alloxan (35 mg/kg b.w.). The training program consisted of a 1h swimming session/day with a load corresponding to 5% of the b.w., five days/week for six weeks. At the end of the training period, the rats were sacrificed and blood was collected for quantification of the serum glucose, insulin, GH, and IGF-1 concentrations. Samples of skeletal muscle were used to quantify the IGF-1 peptide content. The tibias were collected to determine their total area, length and bone mineral content. The results were analyzed by ANOVA with P<0.05 indicating significance. Diabetes decreased the serum levels of GH and IGF-1, as well as the tibial length, total area and bone mineral content in the SD group (P<0.05). Physical training increased the serum IGF-1 level in the TC and TD groups when compared to the sedentary groups (SC and SD), and the tibial length, total area and bone mineral content were higher in the TD group than in the SD group (P<0.05). Exercise did not alter the level of IGF-1 in gastrocnemius muscle in nondiabetic rats, but the muscle IGF-1 content was higher in the TD group than in the SD group. These results indicate that swimming training stimulates bone mass and the GH/IGF-1 axis in diabetic rats.     

2型糖尿病患者骨密度改变的初探

探讨２型糖尿病患者骨密度改变及其机制。方法测定９３例２型糖尿病患者及９０例年龄,体重指数相匹配的健康对照者近端（Ｎｅｃｋ、Ｔｒｏｃｈ、Ｗａｒｄ）及正位腰椎（Ｌ２－Ｌ４）ＢＭＤ,血钙（Ｃａ）、磷（Ｐ）、甲状旁腺激素（ＰＴＨ）、尿ＣｒｏｓｓＬａｐ／Ｃｒ浓度。     

2型糖尿病患者血清胰岛素样生长因子Ⅰ及其结合蛋白与大血管并发症的关系

2型糖尿病(T2DM)合并大血管病变者血清游离胰岛素样生长因子Ⅰ(IGF-I)水平较无大血管病变组降低(P<0·01),胰岛素样生长因子结合蛋白1浓度与WHR、胰岛素抵抗指数呈负相关。表明低IGF-I可能参与糖尿病大血管并发症的发生。胰岛素样生长因子结合蛋白1的浓度反映了胰岛素抵抗状态。     

非小细胞肺癌中IGF1、IGFBP2表达与预后的相关性分析

目的探讨非小细胞肺癌组织胰岛素样生长因子1(IGF1)、胰岛素样生长因子结合蛋白2(IGFBP2),蛋白表达与患者临床病理特征及预后的关系。方法将226例确诊的非小细胞肺癌患者癌组织为非小细胞肺癌组;选取其癌旁正常组织为癌旁对照组。检测癌组织及癌旁正常组织IGF1、IGFBP2蛋白表达水平;分析非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达相关性及其与预后的关系;并分析影响非小细胞肺癌患者预后的因素。结果非小细胞肺癌组IGF1、IGFBP2蛋白高表达率高于癌旁对照组(P<0.05)。非小细胞肺癌患者癌组织IGF1、IGFBP2蛋白表达与肿瘤大小、淋巴结转移、组织分化程度、TNM分期有关(P<0.05)。非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达呈正相关(r=0.472,P<0.05)。IGF1、IGFBP2高表达患者五年生存率(33.33%、29.41%)低于低表达患者(69.23%、73.33%)(P均<0.05)。IGF1高表达、IGFBP2高表达、TNMⅢ～Ⅳ期是影响非小细胞肺癌患者死亡的独立危险因素(P<0.05)。结论 IGF1、...     

肺癌患者胰岛素样生长因子1和胰岛素样生长因子结合蛋白3的表达及其临床意义

目的 分析肺癌患者血清和支气管肺泡灌洗液（BALF）中胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）的表达,探讨其在肺癌诊断和预后中的临床意义.方法 运用免疫放射法检测80例非小细胞肺癌患者和14名健康者（对照组）外周血血清与BALF中IGF-1、IGFBP-3的水平.结果 肺癌组血清和BALF中IGF-1表达显著高于对照组（P＜0.01）,IGFBP-3的表达显著低于对照组（P＜0.05）,同时IGF-1/IGFBP-3升高（P＜0.01）.IGF-1、IGF-1/IGFBP-3在有淋巴结转移、远处转移和TNMⅢ～Ⅳ的肺癌患者血清、BALF中明显高于无转移者和TNMⅠ～Ⅱ期者（P＜0.05）,而IGFBP3下降明显高于无转移者及TNMⅠ～Ⅱ期者（P＜0.05）.肺癌组血清IGF-1、IGFBP-3浓度与BALF中的浓度呈正相关（P ＜0.01）;患者血清BALF中IGF-1与IGFBP-3浓度呈负相关（P＜0.05）.结论 非小细胞肺癌患者血清和支气管肺泡灌洗液中IGF-1、IGFBP-3的表达对肺癌的诊断、判断预后有重要临床意义.     

Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8

Aims/hypothesis Genetic investigations in the spontaneously diabetic (Type 2) Goto Kakizaki (GK) rat have identified quantitative trait loci (QTL) for diabetes-related phenotypes. The aims of this study were to refine the chromosomal mapping of a QTL (Nidd/gk5) identified in chromosome 8 of the GK rat and to define a pathophysiological profile of GK gene variants underlying the QTL effects in congenics.Methods Genetic linkage analysis was carried out with chromosome 8 markers genotyped in a GKxBN F2 intercross previously used to map diabetes QTL. Two congenic strains were designed to contain GK haplotypes in the region of Nidd/gk5 transferred onto a Brown Norway (BN) genetic background, and a broad spectrum of diabetes phenotypes were characterised in the animals.Results Results from QTL mapping suggest that variations in glucose-stimulated insulin secretion in vivo, and in body weight are controlled by different chromosome 8 loci (LOD3.53; p=0.0004 and LOD4.19; p=0.00007, respectively). Extensive physiological screening in male and female congenics at 12 and 24 weeks revealed the existence of GK variants at the locus Nidd/gk5, independently responsible for significantly enhanced insulin secretion and increased levels of plasma triglycerides, phospholipids and HDL, LDL and total cholesterol. Sequence polymorphisms detected between the BN and GK strains in genes encoding ApoAI, AIV, CIII and Lipc do not account for these effects.Conclusions/interpretation We refined the localisation of the QTL Nidd/gk5 and its pathophysiological characteristics in congenic strains derived for the locus. These congenic strains provide novel models for testing the contribution of a subset of GK alleles on diabetes phenotypes and for identifying diabetes susceptibility genes.Electronic Supplementary Material Supplementary material is available in the online version of this article at Abbreviations AIS acute insulin secretion - APO apolipoprotein - Asn asparagin - BN Brown Norway - cM centimorgan - EST expressed sequence tags - GK Goto Kakizaki - GLM general linear model - LIPC hepatic lipase - LOD logarithm of odds ratio - Mb megabase - OLETF Otsuka Long-Evans Tokushima fatty - PL phospholipids - QTL quantitative trait locus/loci - RFPW retroperitoneal fat pad weight - SHR spontaneously hypertensive rat - SNP single nucleotide polymorphism - SPG sum of plasma glucose - SPI sum of plasma insulin - TC total cholesterol - TG triglycerides - UTR untranslated region     

老年代谢综合征患者血胰岛素样生长因子1与代谢综合征的关系

目的了解代谢综合征(metabolic syndrome,MS)患者血胰岛素样生长因子1(IGF1)水平及其与MS的关系。方法按2005年国际糖尿病联盟(IDF)颁布的MS定义,将老年患者465例分为MS组255例和对照组210例。查空腹血糖、胰岛素、C肽、餐后2 h血糖、血脂全套、血IGF1并计算体质指数(BMI)。两组按是否并存糖尿病再分为糖尿病和非糖尿病两个亚组。结果(1) MS组除高密度脂蛋白胆固醇(HDL-C)低于对照组外,其他血液指标均高于对照组(P<0．01);两组IGF1水平与年龄、BMI均呈负相关(P<0．05)。(2)MS糖尿病组IGF1(163．5±128．1)μg／L、胰岛素(14．3±10．5)mU／L高于MS非糖尿病组(114．0±52．6)μg／L、(8．46±4．4)mU／L,C肽(1．1±0．4)μg／L低于MS非糖尿病组(2．5±0．4)μg／L,均为P<0．01;IGF1水平与胰岛素、C肽无相关性,与冠心病呈负相关(P<0．05)。(3)对照糖尿病组IGF1(129．2±49．1)μg／L低于对照非糖尿病组(136．6±80．5)μg／L,胰岛素(14．1±11．7)mU／L、C肽(3．28±2．23)μg／L高于对照非糖尿病组(10．3±6．1)mU／L、(2．9±1．7)μg／L,P<0．01或0．05。对照组IGF1与C肽负相关,与甘油三酯正相关;对照糖尿病组IGF1与胰岛素、C肽负相关(均为P<0．01或0．05)。结论MS患者存在高血IGF1现象,这与单纯糖尿病患者低IGF1不同;MS患者IGF1水平较低时发生冠心病的机率较高。     

男性2型糖尿病患者骨密度变化及其相关因素分析

目的 探讨男性T2DM患者骨密度（BMD）的变化,并分析主要相关因素. 方法 选取 156例男性T2DM患者和104名健康体检者,分为BMI＜25 kg/m2（Nob组）以及BMI≥25 kg/m2 （Ob组）,分别测定两组股骨颈大转子处BMD及T值,比较组间差异并分析T2DM患者BMD的相关因素.结果 （1）两组中T2DM患者（A、C亚组）与健康体检者（B、D亚组）的BMD差异无统计学意义.（2）相关分析表明,T2DM患者的BMD与体重、BMI及WC呈正相关,与Cr呈负相关;与年龄、HbA1c、TC、病程等无相关性.BMI是男性T2DM患者BMD改变的因素（r2=0.361,P＜0.05）. 结论 男性T2DM患者与股骨颈大转子处BMD无相关性.     

2型糖尿病患者骨密度变化及相关危险因素分析

目的研究2型糖尿病（T2DM）患者骨密度（BMD）变化情况。方法测定336例T2DM患者BMD,采用不同诊断标准,统计骨质疏松症（0P）检出率;对比OP组与非OP组生化指标差异并进行相关性分析。结果以低于峰值BMD2．5s及2．0s为诊断标准,OP检出率分别为8．90％和17．26％。BMD与年龄负相关（P〈0．01）,与BMI正相关（P〈0．05）,与女性绝经年数负相关（P〈0．01）。40-49岁组BMD与DM病程相关（P〈0．05）。结论年龄越大、BMI越低,绝经年数越长,越易发生骨质疏松。T-Score≤-2．0SD诊断OP可能适合本地区T2DM患者,但需进一步积累资料证实。     

A role for plasmin in platelet aggregation: Differential regulation of IGF release from IGF–IGFBP complexes?

OBJECTIVES: To determine if plasmin differentially augments platelet aggregation through variable efficiencies of IGF-IGFBP complex cleavage. METHODS: We utilized ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF-II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were performed as controls. RESULTS: We found that IGF-I complexes augmented platelet-mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2 and IGFBP-3 using plasmin revealed that three of the four aggregation findings were explained by the disparate efficiencies of IGFBP proteolysis associated with each IGF. Only IGF-II-IGFBP-2 complex resulted in a finding that could not be explained by the concept of differential regulation of plasmin's proteolysis efficiency by the two IGF ligands. CONCLUSIONS: Our findings demonstrate that the plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the IGF axis.     

Determination of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in serum and plasma: comparisons using the Bland–Altman method

The measurement of circulating insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) have significant implications in the risk assessment of various diseases (e.g. cancer) and growth abnormalities. It is often assumed that values measured in serum and plasma are interchangeable. This study challenges this assumption by comparing determinants using the Bland-Altman method. Blood was obtained from 47 healthy volunteers (age 21-72 years) in serum, heparin plasma and EDTA plasma, and IGF-I, IGF-II, IGFBP-2, and IGFBP-3 measured, and results compared. Mean values for IGF-I, IGF-II, IGFBP-2 and IGFBP-3 determined in all three media were generally comparable; correlations were generally strong and significant (P<0.001). However, the Bland-Altman plots revealed significant lack of agreement for many analytes measured in EDTA plasma compared with serum and heparin plasma. Additionally, the ranges of the limits of agreement were consistently greater for EDTA plasma compared with the other two methods. These findings emphasize the need to standardize methods of collecting blood samples in future epidemiological studies and trials.     

Characterization of the IGF axis in a rat liver-derived epithelial cell line

We have used the techniques of chemical cross-linking, Western blotting and immunoprecipitation-ligand blotting to demonstrate that insulin-like growth factor binding protein-2 (IGFBP-2) is associated with plasma membranes of an epithelial cell line derived from rat liver as well as being secreted into the medium by these cells. We demonstrate that these cells secrete IGF-I, but not IGF-II into serum free medium. Evidence from signalling, cell proliferation and cross-linking experiments indicate that these cells also express cell surface IGF-I receptors. Dose-response experiments indicate an enhanced biological activity of the IGF-I analogue des (1-3) IGF-I compared to wild-type IGF-I in both acute signalling experiments and longer-term (24 h) mitogenic assays. As this IGF-I analogue has lower affinity for IGFBPs, we believe that in this cell culture system, activity of IGF-I may be attenuated in the long and short term by the accumulation of IGFBP-2 in conditioned medium and by the presence of IGFBP-2 associated with the cell membrane and/or ECM.     

高血清胰岛素样生长因子结合蛋白7血症与胰岛素抵抗的相关性研究

目的 研究T2DM患者血清胰岛素样生长因子结合蛋白7（IGFBP7）与坂的相关性。方法选取新诊断T2DM患者（T2DM组）137例和健康体检者（NC组）96名,测定两组FPG、FInS、血脂、C-RP、肿瘤坏死因子a（TNF-a）和IGFBP7。结果T2DM组除TC和LDL-C外,其余指标与NC组比较差异有统计学意义（P〈0．05）。按T2DM组IGFBP7四分位数将其分成4组（Q1～4）,各组间年龄、BMI、C-RP、TNF-a、Fins、HOMA-IR和HOMA-IS差异有统计学意义（P＜0．05）;新诊断T2DM患者IpFBP7与年龄、BMI、C-RP、TNF-a、Fins和HOMA-IR呈正相关（r=0．264、0．173、0．255、0．227、0．192、0．325,P〈0．05）,与HOMA-IS呈负相关（r=-0．324,P〈0．01）。年龄、C-RP、TNF-n和HOMA-IR是影响新诊断T2DM患者IGFBP7水平的独立因素（β’=0．318、0．186、0．239、0．255,P〈0．05）。结论新诊断T2DM患者IGFBP7与年龄、C-RP、TNF-a和HOMA-IR密切相关。     

肝纤维化形成中血管紧张素(1-7)及其转换酶与胰岛素样生长因子结合蛋白2的动态变化

肝脏存在局部肾素-血管紧张素系统(RAS),血管紧张素Ⅱ(AngⅡ)是其主要介质,AngⅡ在肝星状细胞活化与纤维增生中起重要作用.近年发现血管紧张素转换酶2(ACE2)及其代谢产物Ang-(1-7),Ang-(1-7)可通过Mas受体拮抗AngⅡ的作用,引起血管舒张、抑制细胞增殖[1].胰岛素样生长因子结合蛋白2(IGFBP-2)主要由肝实质细胞产生和表达,与肝纤维化的形成关系密切[2].但对Ang-(1-7)、ACE2及IGFBP-2在肝纤维化形成过程中的动态变化报道较少.因此,本实验采用CC14诱导的大鼠肝纤维化模型作为研究对象,探讨ACE2、Ang-(1-7)、IGFBP-2在大鼠肝纤维化形成过程中的动态变化.     

女性2型糖尿病患者骨密度调查与评估

目的观察女性2型糖尿病（T2DM）患者的骨密度（BMD）变化，探讨BMD数据比较的方法。方法选取女性T2DM患者484例，健康女性志愿者868例，测量正侧位腰椎2至4的椎体、左侧股骨颈、大转子和Ward三角区BMD。确立健康女性各骨骼部位BMD随年龄的变化关系，以三次回归模型建立数据库。结果（1）糖尿病组BMD值与正常人比较无统计学差异。（2）与峰值BMD比较，糖尿病组随年龄增加BMD值下降，且受累骨骼部位增加。（3）同年龄组糖尿病和正常人与峰值骨量差值比较，差异无统计学意义。结论T2DM患者BMD变化与正常人群无统计学差异；比较与峰值骨量的差值是判断骨质疏松程度的标准。     

Interleukin-6 and insulin-like growth factor system relationships and differences in the human placenta and fetus from the 35th week of gestation

The integrity of the insulin-like growth factor (IGF) system is essential for normal fetal growth. Cytokine and IGF-IGFBP relationships have been shown in specific tissues, but it is unknown whether these occur in the placenta. We aimed to assess possible differences in the IGF system depending on gestational age (GA) from week 35 to 40, and to study relationships of IL-6 with components of the IGF system in the placenta and newborn infant. We followed 32 normal births and collected whole villous tissue and cord serum. Total RNA was extracted from the placenta samples, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins were assayed in placenta lysates and cord serum using specific commercial kits. Two groups of subjects (Group 1, 35-37 weeks GA, N=12 and Group 2, 38-40 weeks GA, N=20) were studied. In placenta, IGF-I mRNA was more abundant than IGF-II mRNA at all times and together with IGFBP-1mRNA were less expressed at term. IGFBP-2 and IL-6 mRNAs were higher after week 37 GA. IL-6 and IGFBP-2 gene expression were closely related. The corresponding proteins showed similar differences to the genes but IGF-I was undetectable in the lysates, whereas IGF-II was abundant. IGFBP-2 concentrations were very high and greater than those of IGFBP-1. In the newborn, no difference was seen in any cord serum protein after week 35 GA. IGFBP-1 was negatively correlated with parameters of neonatal size. In conclusion, this study reports new insights into IL-6, IGF-IGFBP relationships within the human placenta and shows the importance of comparing subjects with the same GA.