Serum Insulin-like Growth factor-I Levels Research Articles

Relation of insulin‐like growth factor‐IandIGFbinding protein 3 with markers of inflammation: results of a population‐based study

Previous studies in acromegaly and growth hormone deficiency observed inverse associations between insulin-like growth factor-I (IGF-I) levels and inflammatory biomarkers including high-sensitive C-reactive protein (hsCRP), interleukin-6 or fibrinogen. We aimed to assess the relations between IGF-I or IGF binding protein 3 (IGFBP-3) levels and hsCRP, interleukin-6, fibrinogen and white blood cell count (WBC) in a population-based sample. Data from 3480 subjects from the population-based Study of Health in Pomerania (SHIP) were used. IGF-I, IGFBP-3 and inflammatory biomarkers were measured. Analysis of variance (anova), quantile regression models and logistic regression models, adjusted for age, smoking, diabetes mellitus and waist circumference, were performed. anova and/or quantile regression showed inverse associations between IGF-I and hsCRP as well as positive associations between IGF-I and fibrinogen among both sexes. Furthermore, the odds of elevated fibrinogen levels increased with increasing IGF-I levels (per SD IGF-I increase: men: odds ratio (OR) 1·35 [95% confidence interval (CI) 1·04, 1·55]; women: OR 1·44 [95% CI 1·21, 1·71]) in both sexes, whereas the odds of increased hsCRP (women: OR 0·46 [95% CI 0·36, 0·58]) and interleukin-6 (men: odds ratio (OR) 0·77 [95% CI 0·61, 0·96]; women: OR 0·69 [95% CI 0·55, 0·86]) decreased. Serum IGF-I levels are associated with inflammatory biomarkers including hsCRP, interleukin-6 and fibrinogen. Further experimental studies are needed to elucidate the mechanisms underlying the relation between the GH/IGF axis and the inflammatory system.

The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-Cre, PTEN knockout mice

Elevated insulin-like growth factor-I (IGF-I) serum levels and phosphatase and tensin homolog (PTEN) loss are prostate cancer (PCa) risk factors that enhance androgen-responsive and castration-resistant PCa xenografts growth. The impact of suppressed growth hormone (GH)/IGF-I levels on neoplastic initiation of PTEN-deficient prostate epithelia was assessed histologically and by epithelial-to-mesenchymal marker expression in Ghrhr D60G homozygous (lit/lit) and heterozygous (lit/+) pbARR2-Cre, PTEN(fl/fl) (PTEN-/-) mice. How suppressed GH/IGF-I levels impacted growth of PTEN-/- mouse-derived prostate cells (MPPK) was examined by growth and survival signaling of cells cultured in lit/+ or lit/lit serum. Body weight, prostate weight and serum GH and IGF-I levels were reduced in lit/lit relative to lit/+ PTEN-/- littermates. While the anterior lobes of lit/+ PTEN-/- prostates consistently presented swollen, indicative of ductal blockage, the degree of prostatic dysplasia in 15- and 20-week-old lit/lit and lit/+ PTEN-/- mice was indistinguishable as measured by normalized prostatic weight, tissue histology, or probasin, PSP94, E-cadherin, N-cadherin and vimentin expression. However, growth and AKT activation of MPPK cells was decreased when cultured in lit/lit serum as compared with lit/+ serum and restored in lit/lit serum supplemented with IGF-I and, to a lesser extent, GH. These results suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germline variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that these factors may affect the progression of dysplastic phenotype and supports previous studies, indicating that the GH/IGF milieu does impact the growth of PTEN-deficient dysplastic prostatic cells once transformed.

Improvement of insulin resistance following transsphenoidal surgery in patients with acromegaly: correlation with serum IGF-I levels.

The aim of this study was to determine the correlation between the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis and glucose intolerance in acromegaly during the early postoperative period. The study included 20 patients with acromegaly caused by GH-secreting pituitary adenoma who received transsphenoidal surgery in our hospital. Glucose tolerance was evaluated with oral glucose tolerance tests (OGTTs) performed during pre- and early postoperative periods (9 [7-18] days after surgery). Homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index (IGI) were calculated, and correlation analyses were performed between these values and the GH-IGF-I axis. Patients were divided according to postoperative changes of the axis, and glucose tolerance was compared between the groups. In preoperative OGTTs, nine patients had impaired glucose tolerance and two had diabetes mellitus patterns. Postoperatively, significant reduction was observed both in fasting plasma glucose levels (p<0.01) and in HOMA-IR (p<0.01), whereas IGI showed no significant change. HOMA-IR was significantly correlated with serum IGF-I levels both before (r=0.83, p<0.01) and after (r=0.57, p<0.01) surgery, although it was not correlated with serum GH levels. Patients who achieved more than 50% postoperative reduction in serum IGF-I levels showed significant improvement in OGTTs results (p<0.05). In patients with acromegaly, serum IGF-I levels, but not GH levels, were significantly correlated with insulin resistance. Early postoperative improvement of glucose tolerance is observed in patients who achieved postoperative reduction in serum IGF-I levels.

Serum but not cerebrospinal fluid levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) are increased in Alzheimer's disease

Although insulin-like growth factor-I (IGF-I) is of importance for the adult function of the central nervous system (CNS), little is known of the significance of IGF-I in cerebrospinal fluid (CSF) in relation to Alzheimer's disease (AD). A cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), or other dementias (n=15). IGF-I, IGF-binding protein-3 (IGFBP-3), and insulin were measured in serum and CSF. Serum IGF-I level was increased in AD patients and in patients with other dementias compared to healthy controls (P=0.01 and P<0.05, respectively). Serum IGFBP-3 concentration was increased in AD and SMCI patients compared to controls (P=0.001 and P<0.05, respectively). CSF levels of IGF-I and IGFBP-3 as well as serum and CSF levels of insulin were similar in all study groups. In the total study population (n=80), serum levels of IGF-I and IGFBP-3 correlated negatively with CSF β-amyloid₁₋₄₂ (Aβ₁₋₄₂) level (r=-0.29, P=0.01 and r=-0.27, P=0.02, respectively) and in the AD patients (n=32), the increased CSF/serum IGF-I ratio correlated positively with the CSF level of phosphorylated tau protein (P-tau; r=0.42, P=0.02). Patients with AD as well as other dementias had high levels of IGF-I in serum but not in CSF. In AD patients, the IGF-I system was associated with biomarkers of AD disease status.

Effects of lifestyle on plasma levels of the IGF system and the antioxidants coenzyme Q10 and vitamin E in Kenyan rural and urban populations

ObjectiveOvernight fasting blood plasma insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), coenzyme Q10, (CoQ) vitamin E and plasma lipids were compared between a semi-nomadic Samburu population and relatively urbanized cohorts from Nairobi, Kenya. Research design and methods143 middle aged subjects without known diabetes were included. IGF-I and IGFBP-1 were analyzed by RIA, and CoQ and vitamin E by HPLC. Plasma lipid levels were analyzed by standard laboratory methods routinely used in the clinics. ResultsThe age adjusted IGF-I serum levels were low in the Samburu male and female populations, ranging from 0 to −4 IGFSD-score (SDS), and a minor part of the investigated population reaching as low as −5 and −7 SDS. The Nairobi cohorts showed significantly higher values reaching from −2.5 to +1 SDS (P<0.0001). The nomadic Samburu population showed fasting IGFBP-1 values ranging from 30–100μg/l, while that of the urbanized Nairobi cohorts was considerably lower (25–60μg/l) (P<0.0001). CoQ concentrations of the Nairobi cohorts were 1.5–2.0nmol/ml similar to the levels found in several European countries. The Samburu population on the other hand showed extremely high CoQ values ranging from 2 to 9nmol/ml (P<0.0001). Vitamin E levels of the Nairobi group were low (5–20nmol/ml), but the Samburu population had even lower levels ranging from 3 to 15nmol/ml (P<0.0001). Plasma lipid levels such as cholesterol, triglycerides, LDL/HDL, ApoB/ApoA ratios as well as BMI and weight were significantly higher in the Nairobi population (P<0.0001). ConclusionsLow IGF-I and high IGFBP-1 levels of the Samburu cohorts indicate malnutrition. High lipid levels of the Nairobi cohorts indicate that these groups have several risk factors for cardiovascular diseases and diabetes type2.

Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: a retrospective clinical study and review of the literature

Although somatostatin analogues are effective medical therapy for acromegaly, the serum insulin-like growth factor-I (IGF-I) levels remain uncontrolled in 35% of patients. Combined therapy with octreotide LAR and cabergoline has been reported to normalize IGF-I levels in 42-56% of Caucasian patients with acromegaly. However, it remains to be clarified whether combination therapy is effective in Japanese patients and on tumor shrinkage. We conducted a retrospective study on combined therapy in patients with octreotide-resistant acromegaly. Ten patients with acromegaly who showed octreotide-resistance were enrolled in this study. Cabergoline was added in doses of 0.25-2.0mg/week. Serum GH and IGF-I levels and tumor volume were assessed before and after treatment, and factors correlated with effect of the combined therapy were analyzed. Although serum GH levels did not decrease, serum IGF-I levels significantly decreased by 20% after 6 months of combined therapy compared with baseline (p < 0.05). As a result, serum IGF-I levels normalized in 30% of the patients. Tumor volume after combined therapy also significantly decreased (p < 0.01). There were no correlations between the decrease of serum IGF-I levels during combined therapy and the response of GH in a bromocriptine test, random GH, IGF-I, and PRL levels, the tumor volume, and the expression of PRL and dopamine D2 receptor in the tumor. In conclusion, we demonstrated that the addition of cabergoline to octreotide LAR is a beneficial option in Japanese patients with octreotide-resistant acromegaly, irrespective of serum PRL levels and the response of GH levels in a bromocriptine test.

温度、盐度及其互作效应对吉富罗非鱼血清IGF-I与生长的影响

Tilapia,a major freshwater fish species cultured in southern China,takes up an important position in the development of China's aquaculture.Salinity differences have been proven to have clear effects on the growth and physiology in tilapia.Relationship exists between the salinity for optimum growth in fish and their iso-osmotic condition.When salinities shift away from the iso-osmotic point,a reduction in fish growth and feed utilization could be due to more energy consumption used for osmoregulation.Temperature is also a key factor affecting feeding and growth in tilapia.Serum insulin-like growth factor I(IGF-I) in fish has been associated with growth and osmoregulation.In the current experiment,based on central composite experimental design and response surface method,13 experimental runs,each replicated three times,were investigated.The effect of temperature(18—37℃),salinity(0—18) and their interaction on serum IGF-I level,specific growth rate(SGR) and feed efficiency(FE) of GIFT strain Nile tilapia juveniles(Oreochromis niloticus) were studied under laboratory conditions,and the interrelationship between IGF-I to SGR and FE was also investigated.The entire experiment lasted for 8 weeks.The results showed that the linear and quadratic effects of water temperature on serum IGF-I,SGR and FE were statistically significant(P0.05) and the linear and quadratic effects of salinity on serum IGF-I and SGR were also significant(P 0.05).SGR and FE varied with increasing water temperature and salinity in a curvilinear manner.High temperature and high salinity could hinder the increase of SGR and FE.With the increased level of water temperature,serum IGF-I level increased at the beginning and then decreased when temperature was beyond 30℃;serum IGF-I level was lower around the iso-osmotic point.Serum IGF-I level was positively correlated with fish growth and FE,with the R2 being 0.496 and 0.698(P0.05),respectively.The results showed the evidence of higher SGR and FE at high serum IGF-I levels in tilapia.The interactive effects of temperature $salinity on serum IGF-I,SGR and FE were nosignificant(P0.05).Water temperature was more important than salinity in affecting serum IGF-I,SGR and FE.The model equations of SGR,FE and serum IGF-I level using least squares method was obtained,with the R2 as high as 0.949,0.986,0.984,respectively.These models could be used for practical projection.The optimal temperature / salinity combination was obtained utilizing statistical optimization approach: 28.5℃ /8.4,at which the maximal SGR and FE reached 2.29%.d-1 and 0.82,respectively,with the desirability being 0.937.Growth performance of Nile tilapia seemed to be related to the amount of energy expended for osmoregulation.When temperature-salinity deviated from the optimal combination,Nile tilapia has to potentially spend more energy on osmoregulation.These results suggest that the optimum combination of temperature and salinity enhance tilapia growth performance,feeding efficiency and increase serum IGF-I levels.

Insulin-like growth factor I correlates with MELD and returns to normal level after liver transplantation

Insulin-like growth factor I (IGF-I) is produced almost entirely by the liver and is the main promoter of anabolic growth hormone (GH) effects on protein, carbohydrate, and lipid metabolism. IGF-I is significantly decreased in patients with liver cirrhosis. Our objective was to determine the relationship between circulating IGF-I and MELD (Model for End-stage Liver Disease) in cirrhotics subjected to orthotopic liver transplantation (OLT). We also assessed the changes of IGF-I and its major binding protein (IGF-binding protein-3 or IGFBP-3) after OLT. In a prospective study, serum levels of IGF-I and IGFBP-3 of 25 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Seven age-matched healthy male volunteers with normal liver enzymes, albumin, and prothrombin time served as controls. MELD was determined on the day of OLT. For this analysis, extra points were not added for patients with hepatocarcinoma. The cirrhotic group had significantly lower IGF-I (46.7±21.6 ng/mL) and IGFBP-3 (1.0±0.9 ng/mL) levels in the pre-transplant period compared with the controls (208.6±76.5 ng/mL and 4.62±0.93 ng/mL, respectively) (p<0.05). There was a negative correlation between IGF-I or IGFBP-3 and MELD (p<0.001) (ß=-1.750; standard error =2.5054 and ß=-0.038; standard error <0.0001, respectively). IGF-I e IGFBP-3 increased to normal levels after OLT (207.7±82.8 and 4.14±1.1 ng/mL, respectively) (p<0.001). Low levels of IGF-I and IGFBP-3 observed in patients with advanced liver cirrhosis are corrected after OLT. IGF-I and IGFBP-3 correlate negatively with MELD.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Clinical Value of Circulating Lipocalins and Insulin-Like Growth Factor Axis in Pancreatic Cancer Diagnosis

Early diagnosis of pancreatic cancer (PC) in diabetic patients is difficult owing to late presentation of symptoms. Hence, finding a marker to identify cancer stage early would be useful to improve survival. We aimed to determine levels of serum retinol binding protein 4 (RBP-4), neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor I (IGF-I), and its binding protein 3 (IGFBP-3) in patients with PC with preexisting type 2 diabetes. Moreover, we assessed their clinical usefulness in PC diagnosis and their association with tumor severity. Twenty-three patients with PC, 32 diabetic patients, and 20 healthy controls were examined. Preoperative and postoperative samples were obtained from 15 patients with PC. Serum insulin, cancer antigen (CA 19-9), RBP-4, NGAL, IGF-I, and IGFBP-3 levels were estimated by enzyme-linked immunosorbent assay. Significant elevation in the levels of RBP-4 (60.1 [46.3-71.4] ng/mL), NGAL (142 [80-235] ng/mL), and IGF-I (174 [9.3] ng/mL) together with significant reduction in the level of IGFBP-3 (3669 [299] ng/mL) was found in patients with PC. Moreover, RBP-4 and NGAL levels were reduced in postoperative samples compared with preoperative ones. Receiver operating characteristic curve analysis revealed that they can distinguish PC from non-PC cases with significant area under the curve. Retinol binding protein 4, NGAL, IGF-I, and IGFBP-3 are associated with PC in type 2 diabetic patients. They could be useful in distinguishing PC from non-PC cases when used in combination or with cancer antigen.

2．（高齢者向け）アンチエイジングのすすめ

The purpose of anti-aging medical checkups is to evaluate the functional age of the patient, aiming to prevent functional aging and rejuvenate the functional age. In this study, a comparison of the medical checkup results was conducted in elderly groups with different levels of activities of daily living (ADL). There were three groups of subjects; and an independent group that included 43 independently-living subjects (68.9±6.3 years) in the Kyoto Yurin area, a support-requiring group that included 31 subjects (77.8±7.2 years) routinely visiting a day care center and a nursing-requiring group that included 19 subjects (83.7±6.8 years) who were living in a medical care facility for the elderly. We conducted anti-aging medical checkups, and the following five factors were evaluated: muscle mass by the bioelectric impedance method (Physion MD), bone strength by an ultrasonic wave method (A-1000: Yokogawa, AOS-100NW: Aloka), fingertip pulse wave analysis (SDP-100: Fukuda), cognitive function (Wisconsin card sorting test) and the serum insulin-like growth factor-I and dehydroepiandrosterone-sulfate (DHEA-s) level. To calculate the functional age of the subjects, we used the Age Management Check (Ginga Kobo, Nagoya), and the Δage (functional age-chronological age) was analyzed and compared between the groups. The functional ages in the independent group were muscle age, 55.5±7.0; blood vascular age, 65.4±8.5; neural age, 63.6±14.8; hormone age, 70.4±7.6 and bone age, 60.2±14.6 years. As a result of an increase in 1,506 daily steps based on walking instruction with pedometer monitoring, the subjects significantly improved their body weight, BMI, waist size, fasting plasma glucose level and serum DHEA-s in six months. By showing them their functional age, their motivation to participate in the health promotion program was increased, and the compliance was high, with an omission rate of less than 20% in 2.5 years. The support- and nursing-requiring groups showed muscle ages of 58.8±3.3 and 61.9±4.0, blood vascular ages of 75.5±12.6 and 71.8±11.1, neural ages of 86.5±8.8 and 88.5±5.8 and bone ages of 81.0±12.0 and 75.7±12.3, respectively. The Δage analysis in the three groups revealed that the Δneural age increased as the ADL decreased. The Δage analysis indicated that the decreased ADL in the elderly may be mainly associated with their neural function in the factors examined. Anti-aging medical checkups are high in terms of their cost-performance ratio and are easily accepted by the elderly, and are thus recommended for elderly with all grades of ADL.

Methylphenidate and the Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age

BackgroundGrowth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory.ObjectiveTo explore the effects of MP treatment on growth in GH-treated short SGA childrenMethodsAnthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis.ResultsThe SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (±0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (−1.9 SDS and −1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups.ConclusionMP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.

The ratio of insulin-like growth factor-I/insulin-like growth factor–binding protein-3 in sera of patients with hepatitis C virus–related chronic liver disease as a predictive marker of insulin resistance

Recent studies have elucidated a lower level of serum insulin-like growth factor-I (IGF-I) or a decrease in the IGF-I/IGF-binding protein-3 (IGFBP-3) ratio in patients with type 2 diabetes mellitus or hepatic steatosis. Persistent hepatitis C virus (HCV) infection often evokes metabolic abnormalities including hepatic steatosis and insulin resistance. We hypothesized that the relationship between the ratio of IGF-I/IGFBP-3 and the severity of hepatic steatosis or insulin resistance would be observed in patients with HCV-related chronic liver disease (CLD). On the basis of the classifications proposed by Brunt and colleagues (Am J Gastroenterol 1999; 94: 2467-2474), among the 42 enrolled patients with HCV-related CLD, 23 of them had no hepatic steatosis (grade 0), 14 had grade 1 steatosis, and 5 had grade 2 steatosis. The levels of serum IGF-I in the enrolled patients declined in proportion to the severity of hepatic steatosis, whereas serum IGFBP-3 levels did not affect its severity. Therefore, the ratio of IGF-I/IGFBP-3, which corresponds to the circulating free IGF-I status, was significantly lower in those patients with hepatic steatosis (grades 1 and 2) than in those without hepatic steatosis. Serum IGF-I levels significantly correlated with serum zinc levels (r = 0.370, P = .0266), but IGFBP-3 levels did not. However, the linear regression analysis revealed an inverse correlation between the IGF/IGFBP-3 ratio and the value of homeostasis model for assessment of insulin resistance (r =−0.411, P = .0094). These findings suggest that the decline of the circulating free IGF-I level, which derives from zinc deficiency, may contribute to hepatic steatosis and insulin resistance in patients with HCV-related CLD.

Divergence between hepatic insulin-like growth factor (IGF)-I mRNA expression and IGF-I serum levels in Leishmania (Leishmania) infantum chagasi-infected dogs

Visceral leishmaniasis (VL) caused in the New World by Leishmania (Leishmania) infantum chagasi has dog as important peridomestic reservoir in its transmission cycle. Since VL in infected animals is similar to human VL, its study is interesting for human pathology. During Leishmania infection, insulin-like growth factor-I (IGF-I) plays a role in the host-parasite interaction, favoring parasite growth, particularly acting directly on Leishmania. We evaluated IGF-I mRNA expression in different organs/tissues, which was differently modulated in dogs naturally infected by L. (L.) infantum chagasi. We also evaluated the hepatic IGF-I mRNA and serum IGF-I levels in infected dogs. Hepatic mRNA IGF-I expression was higher in the infected dogs than in control animals. However, the serum levels of IGF-I, which are related to the production of this factor in the liver, were reduced in the infected dogs compared with the non-infected controls. Thus, we suggest interference in post-transcriptional processing in IGF-I production in active visceral leishmaniasis.

Insulin-like growth factor I: A biologic maturation indicator

Determination of the maturation level and the subsequent evaluation of growth potential during preadolescence and adolescence are important for optimal orthodontic treatment planning and timing. This study was undertaken to evaluate the applicability of insulin-like growth factor I (IGF-I) blood level as a maturation indicator by correlating it to the cervical vertebral maturation index. The study was conducted with 120 subjects, equally divided into 60 males (ages, 10-18 years) and 60 females (ages, 8-16 years). A lateral cephalometric radiograph and a blood sample were taken from each subject. For each subject, cervical vertebral maturation and IGF-I serum level were assessed. Mean values of IGF-I in each stage of cervical vertebral maturation were calculated, and the means in each stage were statistically compared with those of the other stages. The IGF-I mean value at each cervical vertebral maturation stage was statistically different from the mean values at the other stages. The highest mean values were observed in stage 4, followed by stage 5 in males and stage 3 in females. IGF-I serum level is a reliable maturation indicator that could be applied in orthodontic diagnosis.

Cognitive function in association with sex hormones in postmenopausal women

Several studies have suggested gender differences in cognitive function, but data on the association between sex hormones and cognitive function are contradictory. The aim of our randomized double-blind study was to explore the possible relations between cognitive function and serum levels of sex hormones, oxytocin and insulin-like growth factor-I (IGF-I) in postmenopausal women. Two-hundred healthy postmenopausal women were randomly assigned to receive estrogen, testosterone or placebo treatment for 1 month. The associations of spatial ability, verbal fluency and verbal memory with serum levels of estradiol, testosterone, estradiol/testosterone ratio, androstanediol, oxytocin and IGF-I were analyzed. Spatial ability showed a negative correlation with serum estradiol, estradiol/testosterone ratio, oxytocin levels and a positive association with androstanediol levels. Verbal fluency displayed a negative relationship with serum levels of testosterone, IGF-I and a positive with estradiol/testosterone ratio. Verbal memory displayed a positive correlation to androstanediol. Data suggest that not only absolute levels of sex hormones but also the balance between estrogen and testosterone and their metabolites may be important for cognitive function in women.

12-Month effects of once-weekly sustained-release growth hormone treatment in adults with GH deficiency

The weekly sustained-release recombinant human GH formulation LB03002, showed beneficial effects in GH-deficient (GHD) adults in a previous 26-week double-blind study. Prior studies of long-acting GH preparations in adults have only been conducted for 6 or 8 months, so the effects of longer-term use are unknown; this is important to address, as replacement is given for many years in GHD adults. This open-label, 26-week study extension evaluated longer-term safety and efficacy of LB03002 over 52 weeks in adults with GHD who had previously been randomized to GH, and provides additional safety and efficacy data over 26 weeks in the cohort who had previously been randomized to placebo. Of 147 adults with GHD who completed a preceding study, 136 patients continued in this open-label study to receive LB03002 over an additional 26 weeks. This represented a continuation of long-acting GH for 26 weeks in the cohort who took this medication in the prior study (LB03002 Throughout group), and describes the first use of long-acting GH in the cohort that was randomized to placebo in the prior study (Switched to LB03002 group). The LB03002 dose was adjusted according to serum insulin-like growth factor-I (IGF-I) levels. LB03002 treatment demonstrated mean significant decreases from baseline in fat mass (FM) for both 26 (Switched group, P = 0.001) and 52 weeks (Throughout group, P = 0.002) of 1.11 (1.95) kg and 1.06 (3.16) kg, respectively. Prolonged GH treatment was effective in sustaining the increase in lean body mass (LBM), serum IGF-I and IGFBP-3 levels achieved during the first 26 weeks. Long-term treatment with the sustained-release weekly GH preparation over both 26 and 52 weeks in adults with GHD demonstrated a sustained reduction of FM with a favorable safety profile. This study extends prior knowledge about long-acting GH because it reports the most prolonged treatment of adults with any long-acting GH preparation, thereby confirming the value and safety of such agents for long-term GH replacement.

Growth and IGF-I response of juvenile Nile tilapia (Oreochromis niloticus) to changes in water temperature and dietary protein level

Water temperature and dietary protein level play an important role in influencing the growth and insulin-like growth factor I (IGF-I) in Nile tilapia juveniles. The combined effect of temperature (20–34°C) and dietary protein level (25–50%) on the specific growth rate (SGR), feed efficiency (FE), serum IGF-I level and hepatic IGF-I mRNA level was examined under laboratory conditions by employing central composite design and response surface method. Results showed that the linear effects of temperature and dietary protein level on the SGR, FE, serum IGF-I and hepatic IGF-I mRNA level were significant (P<0.05); the quadratic effects of temperature and dietary protein level on the FE and serum IGF-I were significant (P<0.05). The interaction of temperature and dietary protein level on the FE, serum IGF-I and hepatic IGF-I mRNA level all proved significant (P<0.05). The optimal temperature/dietary protein level combination was determined, i.e., 29.9°C/40.3%, at which the greatest SGR (2.748%/d) and FE (0.775) were simultaneously arrived. Both SGR and FE were linearly correlated with serum IGF-I or hepatic IGF-I mRNA level. These results suggested that optimum combination of temperature and dietary protein level would enhance tilapia growth efficiency and IGF-I would regulate growth and FE.

Measurement of free GH and bioactive IGF-I in non-diabetic haemodialysis patients treated with GH for 7 days

End-stage renal failure (ESRF) patients demonstrate augmented growth hormone (GH) secretion, but normal insulin-like growth factor-I (IGF-I) concentrations, indicating a state of GH resistance. To test this hypothesis, we compared the IGF-I response with exogenous GH in haemodialysis patients and healthy controls, with special focus on free GH and bioactive IGF-I. Ultrafiltered free GH and total GH were measured in serum collected hourly for 24 h at baseline and after 7 days of recombinant human (rh) GH (50 µg/kg/day) treatment in 11 non-diabetic haemodialysis patients and 10 matched controls. Serum levels of bioactive IGF-I (determined by cell-based IGF-I receptor activation assay), total IGF-I and the GH-binding protein (GHBP) were assayed twice daily. At baseline, patients showed elevated total GH (24 ± 5 versus 9 ± 1 µg/L × h, P < 0.02), free GH (21 ± 5 versus 7 ± 1 µg/L × h, P < 0.02), reduced GHBP (1.5 ± 0.3 versus 2.5 ± 0.2 nmol/L, P < 0.01), high-normal total IGF-I (173 ± 18 versus 135 ± 14 µg/L, P = 0.12) and subnormal bioactive IGF-I (2.1 ± 0.3 versus 2.8 ± 0.2 µg/L, P < 0.05) when compared with controls. After 7 days of rhGH treatment, there was a greater GH increase in the non-diabetic haemodialysis patients than in controls (total GH: 293 ± 33 versus 166 ± 13 µg/L × h, P < 0.001; free GH: 284 ± 40 versus 126 ± 15 µg/L × h, P < 0.001). GHB remained unaffected and total IGF-I increased to the same extent in patients and controls (701 ± 87 versus 572 ± 33 µg/L, P = 0.17), whereas bioactive IGF-I tended to be lower in patients (5.37 ± 0.55 versus 6.63 ± 0.25 µg/L, P < 0.10). When adjusting for the actual increments in plasma GH, the ability of exogenous GH to stimulate bioactive IGF-I levels was reduced by ~50% in ESRF (P < 0.02), whereas the response of total IGF-I remained normal (74%; P= 0.18) The study demonstrates that ESRF is associated with markedly elevated serum levels of free GH. Furthermore changes in bioactive, but not immunoreactive, IGF-I indicated that the hepatic sensitivity to GH was reduced by 50% in ESRF patients. Clearly, the physiological importance of our observations awaits further studies, but they suggest that changes in total IGF-I may not necessarily reflect changes in the endogenous activity of IGF-I in ESRF patients on GH treatment.

Insulin-like growth factor-I regulates the neonatal immune response in infection and maturation by suppression of IFN-γ

Disturbances in Insulin-like growth factor-I (IGF-I) and dysregulation in neonatal immune responses have been associated with typical neonatal diseases. Immunosuppression by IGF-I might be a key regulator of neonatal immune responses in infection and maturation. However, information on IGF-I serum levels, IGF-I-receptor (IGF-IR) and effects on functional properties of neonatal immune cells is scarce. Neonatal cord blood samples were stimulated with anti-CD3/anti-CD28, PMA/ionomycin or LPS in a whole-blood assay, while IGF-I serum levels and IGF-I receptor expression were assessed. Furthermore the effect of IGF-I on cytokine expression, apoptosis and the DNA binding activity of AP-1 and NFκB was evaluated. IGF-I serum levels were within normal range. The IGF-I-receptor was present on the surface of cord blood CD3+CD4+lymphocytes and cord blood CD14+monocytes. Upon stimulation the IGF-I-R expression on lymphocytes was significantly upregulated. The addition of IGF-I (100ng/ml) to whole blood cultures inhibited the secretion of IFN-γ from PMA/ionomycin-stimulated cord blood mononuclear cells (CBMC). While IGF-I did not influence apoptosis in our experimental setting, it led to a distinct decrease in anti-CD3/CD28-stimulated DNA binding activity of AP-1 and NFκB. Thus IGF-I may be a key regulator of neonatal immune responses in maturation processes and inflammation by suppressing proinflammatory Th1 responses. Future in vivo studies need to elucidate whether disturbances of the IGF-I serum level and IGF-IR expression are associated with susceptibility for infections and subsequent diseases in neonates.