Serum Total Insulin-like Growth factor-I Research Articles

Effect of hyperinsulinemia during hemodialysis on the insulin-like growth factor system and inflammatory biomarkers: a randomized open-label crossover study

BackgroundA marked reduction in serum levels of bioactive insulin-like growth factor-I (IGF-I) has been observed in fasting hemodialysis (HD) patients during a 4-h HD session. The aim of the present study was to investigate the beneficial effect of hyperinsulinemia during HD on bioactive IGF-I and inflammatory biomarkers.MethodsIn a randomized cross-over study, 11 non-diabetic HD patients received a standardised HD session with either: 1) no treatment, 2) glucose infusion (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (10% glucose added 30 IU NovoRapid® per litre, 2.5 mL/kg/h). Each experiment consisted of three periods: pre-HD (−120 to 0 min), HD (0 to 240 min), and post-HD (240 to 360 min). A meal was served at baseline (−120 min); infusions were administered from baseline to 240 min. The primary outcome was change in bioactive IGF-I during the experiment. Secondary outcomes were changes in high-sensitivity C-reactive protein, interleukin-1β, interleukin-6, and tumor necrosis factor α. Comparisons were performed using mixed-model analysis of variance for repeated measures.ResultsFrom baseline to the end of study, no significant differences were observed in the changes in either serum bioactive IGF-I or total IGF-I between study days. Overall, serum bioactive IGF-I levels rose above baseline at 120 to 300 min with a maximum increase of 20% at 120 min (95% confidence interval (CI), 9 to 31%; p < 0.001), whereas total IGF-I levels rose above baseline at 180 to 300 min with a maximum increase of 5% at 240 min (95% CI, 2 to 9%; p = 0.004). A significant difference was observed in the changes in serum IGF-binding protein-1 (IGFBP-1) between study days (p = 0.008), but differences were only significant in the post-HD period. From baseline to the end of HD, no significant difference was observed in the changes in serum IGFBP-1 levels between study days, and in this time period overall serum IGFBP-1 levels were below baseline at all time points with a maximum decrease of 51% at 180 min (95% CI, 45 to 57%; p < 0.001). None of the investigated inflammatory biomarkers showed any differences in the changes over time between study days.ConclusionsPostprandial insulin secretion stimulated the IGF-system during HD with no further effect of adding glucose or glucose-insulin infusion. Hyperinsulinemia during HD had no effect on biomarkers of inflammation.Trial registrationClinicalTrials.gov registry: NCT01209403

Association between serum insulin-like growth factor I or IGF-binding protein 3 and estimated glomerular filtration rate: results of a population-based sample

BackgroundInsulin-like growth factor I (IGF-I), which is mostly carried in blood by IGF-binding protein 3 (IGFBP-3), was associated to the glomerular filtration rate and chronic kidney disease in a multiethnic study among US adults. The aim of the present study was to investigate whether serum IGF-I or IGFBP-3 are associated with estimated glomerular filtration rate (eGFR) in a population-based study of Caucasian adults.MethodsData from 4028 subjects (2048 women) aged 20 to 81 years from the Study of Health in Pomerania (SHIP) were analyzed. Total serum IGF-I and IGFBP-3 concentrations were determined by chemiluminescence immunoassays and categorized into sex- and age-specific quartiles.ResultsAfter adjusting for age, waist circumference and type 2 diabetes mellitus, analysis of variance (ANOVA) revealed inverse associations between serum IGF-I concentrations and eGFR in men as well as between serum IGFBP-3 concentrations and eGFR in men and women. Logistic regression analyses confirmed these findings and showed that high IGF-I or IGFBP-3 concentrations were associated with an increased risk of decreased eGFR (<60 mL/min/1.73 m2) in men or women. These relations became stronger when lower eGFR cut-offs were used for the analyses.ConclusionOur data revealed associations of increased serum IGF-I concentrations and decreased eGFR in men but not in women and an association of increased serum IGFBP-3 concentrations and decreased eGFR in both sexes.

All-cause mortality and serum insulin-like growth factor I in primary care patients

Objective Previous population-based studies provided conflicting results regarding the association of total serum insulin-like growth factor I (IGF-I) and mortality. The aim of the present study was to assess the relation of IGF-I levels with all-cause mortality in a prospective study. Design DETECT (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment) is a large, multistage, and nationally representative study of primary care patients in Germany. The study population included 2463 men and 3603 women. Death rates were recorded by the respective primary care physician. Serum total IGF-I levels were determined by chemiluminescence immunoassays and categorized into three groups (low, moderate, and high) according to the sex- and age-specific 10th and 90th percentiles. Results Adjusted analyses revealed that men with low [hazard ratio (HR) 1.70 (95% confidence interval [CI] 1.05–2.73), p = 0.03] and high [HR 1.76 (95% CI 1.09–2.85), p = 0.02] IGF-I levels had higher risk of all-cause mortality compared to men with moderate IGF-I levels. The specificity of low IGF-I and high IGF-I levels increased with lower and higher cut-offs, respectively. No such association became apparent in women. Conclusions The present study revealed a U-shaped relation between IGF-I and all-cause mortality in male primary care patients.

Hypoglycemia due to Ectopic Secretion of Insulin-Like Growth Factor-I in a Patient with an Isolated Sarcoidosis of the Spleen

Hypoglycemia is reported to be one of the manifestations of a patient with hypothalamic sarcoid infiltrates due to impaired counter-regulation of glucose. But, without hypothalamic lesion, patients with sarcoidosis would not be expected to have hypoglycemia. We recently identified a patient with an isolated sarcoidosis of the spleen who had experienced frequent fasting hypoglycemia which completely disappeared after splenectomy. During hypoglycemia, serum insulin was undetectable. Endocrinological examination revealed no abnormality. The objective was to investigate whether the patient's hypoglycemia was due to ectopic secretion of an insulin-mimetic factor by the splenic sarcoidosis. Serum insulin-like growth factor-I (IGF-I) and IGF-II were measured by RIA. Serum visfatin and free IGF-I were by ELISA. A high molecular weight form of IGF-II, termed "big" IGF-II, was identified by Western blotting. Tissue IGF-I was quantified by real time RT-PCR after RNA extraction. Before operation, total and free serum IGF-I, serum IGF-II and serum visfatin were within reference range. Big IGF-II was not detected in patient's serum extract. After operation, hypoglycemia did not recur and serum insulin returned to normal, while serum IGF-I decreased by half the preoperative level. RT-PCR revealed that mRNA level of IGF-I in the sarcoidosis tissue was about 1.8-fold greater than that in the normal spleen tissue. These data suggest that ectopic secretion of IGF-I by the splenic sarcoidosis and its direct access to the liver via the portal vein might cause fasting hypoglycemia mainly by suppressing hepatic gluconeogenesis.

Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer's disease patients treated with the neurotrophic agent Cerebrolysin

According to current scientific knowledge, excess tumour necrosis factor-α (TNF-α) and low insulin-like growth factor-I (IGF-I) are pathogenic-risk factors that constitute therapeutic targets for Alzheimer's disease (AD). Changes in serum TNF-α, total and dissociable IGF-I levels were determined by ELISA in 207 AD patients completing a 24-wk, double-blind, placebo-controlled trial to evaluate the effects of the neurotrophic compound Cerebrolysin (Cere: 10, 30 or 60 ml for 12 wk). At week 24, Cere reduced TNF-α and enhanced dissociable IGF-I with respect to placebo in a dose-related manner. TNF-α decreased in parallel with behavioural disturbances. Increases in total IGF-I were induced by 60 ml Cere and correlated significantly with improvements in global function, disabilities and behaviour in late-onset AD patients. These results showing for the first time the opposite influence of one anti-dementia treatment on serum TNF-α and IGF-I suggest the contribution of both factors to the clinical effects of Cere, and probably other drugs.

Correlates of Serum Leptin and Insulin-like Growth Factor-I Concentrations in Normal Weight and Overweight/Obese Iranian Women

Leptin and insulin-like growth factor-I (IGF-I) are two interrelated hormones that are implicated in the development or progression of coronary artery disease (CAD) and some cancers. The aim of this study was to investigate the relation between serum leptin and total IGF-I concentrations and to identify their correlations with age or anthropometric and body composition variables in healthy normal weight and overweight/obese Iranian women. The percent of body fat (BF%), fat mass (FM), fat-free mass (FFM), and waist/hip ratio (WHR) were determined in 51 healthy normal weight (body mass index [BMI] 18.5-24.9 kg/m(2)) and 50 overweight/obese (BMI > or = 25 kg/m(2)) Iranian reproductive-age women. Serum leptin and total IGF-I concentrations were measured by double-antibody sandwich assay and enzyme-linked immunosorbent assay (ELISA), respectively. Statistical analysis was performed by Mann-Whitney U test and Spearman's rank-correlation test. Multivariate linear regression analysis was performed with ranked-transformed data to obtain partial correlation coefficient. In this group of healthy, premenopausal Iranian women, variance of serum leptin concentration was independently explained by FM (partial rho = 0.295, p < 0.01), and variance of the total IGF-I concentration was explained by age (partial rho = -0.214, p = 0.037) and BMI (partial rho = 0.229, p = 0.026). Overweight/obese women had higher leptin and total IGF-I concentrations than normal weight women (p < 0.01). The serum leptin and total IGF-I concentrations were differentially correlated with age and anthropometric and body composition variables in the two groups. Whereas in normal weight women, leptin was negatively related to BMI (partial rho = -0.356, p = 0.015), in overweight/obese women, BMI, BF%, and FM independently contributed to the serum leptin variability (partial rho = 0.370, p = 0.013; partial rho = -0.320, p = 0.034; partial rho = 0.421, p < 0.01, respectively). There was a weak association between age and total IGF-I concentration in normal weight women, which did not reach statistical significance (partial rho = -0.255, p = 0.091). None of the variables was associated with the total IGF-I in overweight/obese women (p > 0.05). Although the studied anthropometric and body composition variables could explain approximately half of the leptin variance in Iranian women, they explained only a small proportion of total IGF-I variability. Our results indicated that the serum leptin and total IGF-I concentrations are differentially regulated in healthy normal weight and overweight/obese Iranian women.

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.

Utility of Free IGF-I Measurements

For nearly 30 years, the endogenous bioactivity of insulin-like growth factor I (IGF-I) has been estimated by its circulating concentrations of immunoreactive IGF-I, obtained after either removal or inactivation of the IGF-binding proteins (IGFBPs), and today serum/plasma total IGF-I serves as a useful parameter in the diagnosis and clinical control of growth hormone (GH) disorders. Different assays for the measurement of free, unbound IGF-I were introduced more than a decade ago. Nevertheless, this measurement remains controversial, and in daily clinical practice serum total IGF-I has retained its position as the most widely used IGF-related measurement in GH disorders. This review will provide a survey of data on free versus total IGF-I, with particular reference to GH disorders. As it will be clear, there is reasonable clinical evidence to conclude that both in the diagnosis of as well as during treatment of patients with GH disorders, serum/plasma total IGF-I should remain the primary IGF-related measurement. However, in certain patients the inclusion of free IGF-I may be useful and therefore, some guidelines for the inclusion of free IGF-I measurements will be given.

Effect of Physical Fitness and Endurance Exercise on Indirect Biomarkers of Recombinant Growth Hormone Misuse: Insulin-Like Growth Factor I and Procollagen Type III Peptide

Serum insulin-like growth factor-I (IGF-I) and procollagen type III peptide (P-III-P) have been proposed as indirect biomarkers of rhGH misuse in sports. The purpose of the present study was to investigate concentrations of these biomarkers in athletes at different levels of physical fitness and endurance exercise. Serum total IGF-I and P-III-P were measured in 96 elite athletes of various sports along the training season; in 21 recreational athletes at baseline non-exercising conditions and in another 129 recreational athletes before and after long-distance races (10 and 21 km). No differences were evidenced for IGF-I concentrations, but statistically higher values of serum P-III-P were found in elite athletes compared to recreational ones. Among elite athletes, the specific sport did not affect serum IGF-I. However, P-III-P was statistically higher in the sport performed by the youngest athletes (rhythmic gymnastics), even after correction of the logarithm of the concentration by the reciprocal of age. Over the training season, the within-athlete variabilities of IGF-I and P-III-P in elite athletes were low (22.8 % and 21.7 %, respectively). Recreational athletes taking part in a 21 km competition race showed a significant increase in serum values of IGF-I and P-III-P immediately after the event. Exercise workload and age had a significant effect on serum concentration of P-III-P, while age alone affected IGF-I serum concentrations. Therefore, athlete's reference concentration ranges for doping detection should include subjects from as many different ages and sports as possible.

The insulin-like growth factor system and Type 1 diabetic retinopathy during pregnancy

Aims/Hypothesis To find out whether the levels of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), highly phosphorylated IGFBP-1 (hpIGFBP-1), and IGF binding protein-3 (IGFBP-3) are related to the progression of diabetic retinopathy (DR) during pregnancy and postpartum. Methods In a prospective study of 42 pregnant women with Type 1 diabetes and 9 nondiabetic controls, DR was graded from fundus photographs. Levels of serum total IGF-I and two different phosphoisoform patterns of IGFBP-1 and IGFBP-3 were measured during the first and third trimester of pregnancy and 3 months postpartum. Results Both the levels of serum total IGF-I ( P<.0001) and IGFBP-3 ( P=.003) were lower in the diabetic than in the nondiabetic women during pregnancy and postpartum (repeated-measures ANOVA between the groups). Additionally, the IGF-I and IGFBP-3 levels tended to be lower in the diabetic women with more severe DR at baseline than in those with less severe DR. There were no statistically significant differences in the levels of IGF-I and IGFBP-3 in the diabetic women with progression of DR compared with those without. No statistical differences appeared in the IGFBP-1 phosphoisoform patterns between the groups. Conclusions/Interpretation In diabetic women, mean serum levels of IGF-1 and IGFBP-3 are lower than in nondiabetic controls during pregnancy and/or postpartum. Because there was no clear connection between the IGF system and progression of DR during pregnancy, it is unlikely that these substances mediate the tendency of DR to progress during pregnancy.

Effects of pure ethanol and alcopops on glucose, insulin, and the insulin-like growth factor system in healthy subjects

Introduction Alcohol induces disturbances in insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) levels. The aim of the present study was to compare pure ethanol and alcopop effects on total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, insulin and plasma glucose levels in healthy subjects. Methods Five males and seven females (21–51 years) consumed pure ethanol and alcopops with identical alcohol content in a cross-over design after 6 h fasting. Blood samples were obtained for determination of serum ethanol and plasma glucose at 0, 30, 60, 90, 120 and 180 min. Serum total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, and insulin were measured at 0, 60 and 180 min. Results Area under the curve for serum ethanol concentration was significantly less following alcopop compared to pure ethanol (1124 ± 201 vs. 1691 ± 359 mmol/L h, P < 0.01). Serum insulin and glucose levels were unchanged by ethanol while alcopop intake was followed by a transient increase in glucose and insulin levels ( P < 0.05). Pure ethanol and alcopop reduced free IGF-I levels by the end of the study period ( P = 0.05). IGFBP-1 and the IGF-I:IGFBP-1 complex increased following ethanol intake ( P < 0.05) while only a small transient IGFBP-1 increase was observed following alcopop intake. No change in total IGF-I was observed. Conclusion Both drinks resulted in reduced free IGF-I levels, however, only pure ethanol increased IGFBP-1 and the IGF-I:IGFBP-1 complex. Alcopop intake was associated with a transient increase in IGFBP-1 and unchanged IGF-I:IGFBP-1 complex levels probably due to marked changes in insulin and glucose levels.

Circulating osteoprotegerin and receptor activator of NF‐κB ligand system are associated with bone metabolism in middle‐aged males

Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF-kappaB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG-RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG-RANKL system and bone mineral metabolism in males. Serum concentrations of OPG, RANKL, oestradiol, total testosterone and IGF-I and bone mineral density (BMD) were measured in 80 Korean males aged 42-70 (mean age, 54.5 year). Enzyme-linked immunosorbent assays were used to determine the serum concentrations of OPG and RANKL. Serum concentrations of oestradiol, total testosterone, IGF-I and bone turnover markers were determined using standard methods. BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. We observed a significant negative correlation between the serum OPG levels and lumbar spine BMD (r =-0.259, P < 0.05) in Spearman correlation analysis. Serum OPG levels and RANKL/OPG ratios were found to be significantly correlated to the serum osteocalcin levels (r =- 0.254, P < 0.05; r = 0.264, P < 0.05) in Spearman correlation analysis. Serum OPG levels were found to be negatively correlated with serum oestradiol levels (r =-0.319, P < 0.01) in Spearman correlation analysis. In addition, a significant positive correlation was found between serum RANKL/OPG ratios and oestradiol levels (r = 0.374, P < 0.001) in Spearman correlation analysis. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG levels or RANKL to OPG ratios in Spearman correlation analysis. In a multiple regression analysis, age, body mass index (BMI), and serum OPG levels were identified as a significant predictor for lumbar spine BMD, and age, BMI, serum OPG and RANKL levels for femoral neck BMD. In another multiple regression analysis, only serum oestradiol level was identified as a significant predictor for serum OPG or RANKL levels. In contrast, Serum total testosterone and IGF-I levels were not correlated with serum OPG or RANKL levels in multiple regression analysis. Our data show that the circulating OPG-RANKL system is associated with bone metabolism in the male populations. Also, our data suggest that OPG and RANKL may be mediators of the effects of oestradiol in male bone metabolism.

Longitudinal Associations of Age, Anthropometric and Lifestyle Factors with Serum Total Insulin-Like Growth Factor-I and IGF Binding Protein-3 Levels in Black and White Men: the CARDIA Male Hormone Study

Abstract Although several studies have assessed cross-sectional correlates of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3), there are no longitudinal studies of the correlates of long-term changes in these measures. We examined the 8-year longitudinal associations of age, body mass index (BMI), waist circumference, physical activity, number of cigarettes smoked per day, and alcohol intake with serum total IGF-I and IGFBP-3 concentrations in 622 Black and 796 White male participants of the Coronary Artery Risk Development in Young Adults Study who were ages 20 to 34 years at the time of the first IGF measurement. In generalized estimating equation analyses, IGF-I decreased by 5.6 and 5.9 ng/mL per year increase in age for Black and White men, respectively (P&amp;lt; 0.0001), and there was an age-related decline in IGFBP-3 that was stronger in Whites (P &amp;lt; 0.0001) than Blacks (P = 0.21). Average IGF-I (β = −17.51 ng/mL) and IGFBP-3 (β = −355.4 ng/mL) levels across all three exams were lower in Blacks than Whites (P &amp;lt; 0.0001). Increased BMI was associated with decreased IGF-I (P &amp;lt; 0.0002), but was not associated with IGFBP-3. There were no meaningful associations with waist circumference. Increased physical activity was associated with a decrease in IGFBP-3 (P &amp;lt; 0.05), but was not associated with IGF-I. In White men, there were weak inverse associations between the number of cigarettes smoked per day with IGF-I (P=0.15) and with IGFBP-3 (P = 0.19), and in Black men, increased alcohol intake was associated with a decrease in IGF-I (P = 0.011). In conclusion, these results support an age-related decline and Black-White difference in serum IGF-I and IGFBP-3 levels. Importantly, they suggest that IGF-I and/or IGFBP-3 levels could be influenced by changes in BMI, and perhaps by physical activity, alcohol intake, and cigarette smoking.

Low free and total insulinlike growth factor I (IGF-I) and IGF binding protein-3 levels in chronic inflammatory bowel disease: partial normalization during prednisolone treatment

OBJECTIVES: Catabolism and growth impairment are well known complications of chronic inflammatory bowel disease (CIBD). This may be caused by disease activity itself and/or the medical treatment, which may lead to changes in the growth hormone and insulinlike growth factor I (IGF-I) axis. Interest has focused on corticosteroids, as they are known to influence the growth hormone/IGF-I axis. METHODS: The aim of the present study was to examine changes in total and free IGF-I, IGF binding proteins (IGFBPs), and IGFBP-3 protease activity in 10 patients with severe acute activity in colon CIBD before and during high dose prednisolone treatment (1 wk) and 3 months tapering. Eight healthy subjects served as controls. RESULTS: Total and free IGF-I were significantly reduced by 35% and 53%, respectively, before prednisolone treatment ( p < 0.05), and free IGF-I remained reduced even by the end of the study period relative to controls ( p < 0.05). IGFBP-3 was reduced by 16% before ( p < 0.05), with normalization during prednisolone treatment and tapering relative to controls. There was no evidence of increase in IGFBP-3 protease activity. IGFBP-1 was increased before and tended also to be increased during prednisolone treatment and tapering. CONCLUSIONS: Marked changes in serum total and free IGF-I and IGFBPs were demonstrated in patients with severe exacerbation of CIBD without complete normalization during high dose prednisolone treatment and tapering. These changes may partly be involved in the catabolism of active CIBD patients.

Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans.

The mechanism(s) of load-induced muscle hypertrophy is as yet unclear, but increasing evidence suggests a role for locally expressed insulin-like growth factor I (IGF-I). We investigated the effects of concentric (CON) vs. eccentric (ECC) loading on muscle IGF-I mRNA concentration. We hypothesized a greater IGF-I response after ECC compared with CON. Ten healthy subjects (24.4 +/- 0.7 yr, 174.5 +/- 2.6 cm, 70.9 +/- 4.3 kg) completed eight sets of eight CON or ECC squats separated by 6-10 days. IGF-I, IGF binding protein-4 (IGFBP-4), and androgen receptor (AR) mRNA concentrations were determined in vastus lateralis muscle by RT-PCR before and 48 h after ECC and CON. Serum total testosterone (TT) and IGF-I were measured serially across 48 h, and serum creatine kinase activity (CK), isometric maximum voluntary contraction (MVC), and soreness were determined at 48 h. IGF-I mRNA concentration increased 62% and IGFBP-4 mRNA concentration decreased 57% after ECC (P < 0.05). Changes after CON were similar but not significant (P = 0.06-0.12). AR mRNA concentration increased (P < 0.05) after ECC (63%) and CON (102%). Serum TT and IGF-I showed little change. MVC fell 10% and CK rose 183% after ECC (P < 0.05). Perceived soreness was higher (P < 0.01) after ECC compared with CON. Results indicate that a single bout of mechanical loading in humans alters activity of the muscle IGF-I system, and the enhanced response to ECC suggests that IGF-I may somehow modulate tissue regeneration after mechanical damage.

Age-related serum levels of insulin-like growth factor-I, -II and IGF-binding protein-3 following myocardial infarction.

Aging retards the repair process by decreasing hormone secretion from the somatotrophic axis, which plays a major role in tissue reconstruction after injury. The aim of this study was to determine the effect of aging on serum insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding protein-3 (IGFBP-3) levels following myocardial infarction (MI). For four consecutive days, we monitored the variation of serum IGF-I, IGF-II and IGFBP-3 concentrations in 26 patients aged 19-71 years who were diagnosed with MI. Serum IGF-I, IGF-II and IGFBP-3 were measured daily by double antibody radioimmunoassay. Daily serum IGF-I concentrations showed a significant negative correlation with age (r = -0.528, P< 0.001). Total serum IGF-I was significantly (P = 0.002) higher in the younger age group (patients under 50 years) compared to the older group (50 years and over); 206 +/- 16 ng/ml vs 136 +/- 12 ng/ml. During this investigation, younger patients (under 50 years) showed no significant daily variations in IGF-I levels compared to older patients (50 years and over) who presented a significant decline (P = 0.012). Total serum IGF-II in both groups decreased significantly with time. Total serum IGFBP-3 in the younger age group was significantly higher (P = 0.046) than in the older age group (3.42 +/- 0.18 microgram/ml vs 2.95 +/- 0.13 microgram/ml). MI patients in both groups showed significantly lower IGF-I and IGF-II (IGFs) with higher IGFBP-3 compared to age- and sex-adjusted levels of normal adults (controls). The present results confirm that age and cardiac condition affect IGFs and IGFBP-3 levels. We are inclined to believe that older patients with a cardiac condition are less able to maintain their blood IGF-I levels during the recovery period compared to younger patients. Given the biological impact of IGF-I on regeneration, this could explain why older patients take longer to recover and heal poorly in comparison to younger patients.

Effect of hyperthyroidism on insulin-like growth factor-I (IGF-I) and IGF-binding proteins in adolescent children.

A study was performed on adolescent hyperthyroid patients to determine the effects of hyperthyroidism on insulin-like growth factor (IGF)-I and its binding proteins. Serum concentrations of immunoreactive total and free IGF-I, and IGF binding protein (IGFBP)-2 and IGFBP-3 were determined before and after correction of hyperthyroidism in eight patients with Grave's disease and compared to control patients matched for age, sex and pubertal stage. The concentration of serum total IGF-I was not significantly different in the hyperthyroid state and euthyroid state, and did not differ significantly from euthyroid controls. IGFBP-2 levels were elevated three-fold in hyperthyroid patients at the time of diagnosis of hyperthyroidism compared to control subjects, and fell significantly during treatment. There was also a significant positive correlation between serum IGFBP-2 concentrations and thyroxine (T4) concentrations in all subjects. Serum IGFBP-3 concentrations were also elevated in hyperthyroid subjects and normalized with correction of the hyperthyroidism. There was also a positive correlation between serum T4 and IGFBP-3 concentrations in all subjects. Despite the hyperthyroid-induced elevations in IGFBP-2 and -3, no significant difference in the serum concentration of free IGF-I before or after correction of the hyperthyroid condition was observed. We conclude that hyperthyroidism does not cause alterations in the serum concentrations of either free or total IGF-I. However, both serum IGFBP-2 and IGFBP-3 concentrations were elevated during hyperthyroidism and correlated with serum T4 levels. These abnormalities reversed with normalization of thyroid function.

Differential effect of fasting on IGF-BPs in serum of young and adult rats and its implication to impaired skin GAG content.

During fasting or aging of animals there is a decreased content of skin glycosaminoglycans (GAGs). It has been found that the skin of adult rats contains about 60% of GAGs found in the skin of young animals. Fasting of both groups of animals (young and adult) resulted in decrease of GAG content. However, GAG content in the skin of fasted young rats decreased by 30% and in fasted adult rats by 15% only, compared to fed animals, respectively. The mechanism for the phenomena is not known. We considered insulin-like growth factor-I (IGF-I) as a potential candidate involved in regulation of GAG biosynthesis in both experimental models of animals. Adult rat sera were found to contain about 75% of IGF-I recovered from young rat sera. Fasting of both groups of animals resulted in dramatic decrease in serum IGF-I levels to about 50% of initial values. Since IGF-I activity and IGF-I serum half-life depends on the level of specific IGF-binding proteins (IGFBPs) we determined (i) relationship between main groups of IGFBPs, namely high molecular weight binding proteins (HMWBPs) and low molecular weight binding proteins (LMWBPs) and (ii) the amounts of IGF-I bound to respective proteins in the sera of all experimental animals. Control young rat serum was found to contain about 90% of HMWBPs and about 10% of LMWBPs as determined by ligand binding assay. In contrast, control adult rat serum contained about 60% of HMWBPs and about 40% of LMWBPs. Fasting of both groups of animals resulted in significant increase in serum levels of LMWBPs. Control young rat serum was found to contain about 8% IGF-I bound to LMWBPs while serum of control adult rats contained 18% IGF-I bound to these proteins. In sera of fasted young animals however, about 75% of the bound IGF-I was recovered from LMWBPs (about 60% of total serum IGF-I) while in sera of fasted adult animals only about 56% of the bound IGF-I was recovered from LMWBPs (about 50% of total serum IGF-I). Evidence was provided that during fasting of both groups of animals there is a significant decrease in serum BP-3 and dramatic increase in serum BP-1 concentrations, compared to respective controls. However, the concentration of BP-1 in serum of fasted young rats was increased by about 60 fold while in serum of fasted adult rats only by about 10 fold, compared to respective control animals. Negative correlation between skin GAG content and LMWBPs derived IGF-I during fasting of young (r = -0.943, p < 0.001) and adult ( r = -0.571, p < 0.01) rats was found. The data presented suggest that the effects of aging and fasting on decreased skin GAG content may be due to induction of LMWBPs that are known to (i) inhibit IGF-I dependent function and (ii) increase clearance of IGF-I from circulation. However, the effects of fasting are distinct in respect to young and adult rats suggesting that mechanisms involved in regulation of IGF-I bioactivity during aging are more complex that during fasting.

Hepatic Histidase Gene Expression Responds to Protein Rehabilitation in Undernourished Growing Rats

We studied the effect of nutritional rehabilitation with a 6, 18 or 50% casein diet in undernourished rats on histidase (Hal) expression. Undernutrition was induced by feeding rats a 0.5% casein diet for 5 wk. Over this period, growth, serum total proteins and insulin-like growth factor-I (IGF-I) levels were significantly lower than those of rats that freely consumed an 18% casein diet. During this period, undernutrition also significantly reduced Hal activity and Hal-mRNA concentration. Nutritional rehabilitation for 21 d with a 6% casein diet did not change any of these variables. Nutritional rehabilitation with an 18 or 50% casein diet for 1 d initiated the restoration of Hal activity and mRNA concentration. After 10 d of consuming 18 or 50% casein diets, Hal activity was 5- and 14-fold, and mRNA concentration was 8.5- and 23-fold higher, respectively, than in the protein-undernourished group (PU). During this period, body weight, total serum proteins and IGF-I levels were also significantly (P < 0.05) higher than those of the PU group. At the end of 21 d of rehabilitation with an 18 or 50% casein diet, Hal activity was 14- and 31-fold higher and Hal mRNA concentration was 10- and 24-fold higher, respectively, than in the PU group. In conclusion, our data showed that rehabilitation of undernourished rats with a 6% casein diet was not sufficient to re-establish growth indicators, Hal activity or gene expression, and that nutritional rehabilitation with an 18 or 50% casein diet effectively re-established body weight , biochemical variables and the capacity of histidase gene expression to eliminate the excess of protein.

Insulin-like growth factor–I in women with hydatidiform mole and in normal pregnancy

Objective: To compare molar and placental tissue insulin-like growth factor–I (IGF-I) levels and IGF-I messenger RNA (mRNA) expression and maternal serum IGF-I levels in molar and normal pregnancies of the same gestational length. Methods: Tissue and serum total IGF-I were measured by radioimmunoassay, and tissue IGF-I mRNA expression was measured by a solution hybridization technique in samples from seven patients with hydatidiform mole in gestational weeks 8 through 14 and from 12 women with normal placentas undergoing induced abortion during weeks 8 through 12. Results: Tissue and serum total IGF-I levels and tissue IGF-I mRNA expression were significantly lower in molar pregnancies than in pregnancies with normal placenta. Conclusion: The lower levels of both IGF-I mRNA and of the IGF-I protein itself in hydatidiform mole indicates that the regulation of expression of IGF-I is on the transcriptional level. This finding may reflect a decreased production of the placental growth hormone variant in molar tissue.