Increase In Insulin-like Growth factor-I Levels Research Articles

Higher Peak Height Velocity in Early Maturing Girls Depends on Insulin rather than Fat Mass or IGF-I

Abstract Objective Age at pubertal onset has decreased over the recent decades. Early maturing girls have longer puberty duration, and higher peak height velocity (PHV) than late maturing girls. To what extent this is generated by increased insulin-like growth factor-I (IGF-I), fat mass or fasting insulin levels is currently unknown. Design, setting, participants A population-based study – part of the COPENHAGEN puberty study - longitudinal part. Eighty-one girls evaluated biannually for a median of 10 (2-15) visits for a total of 815 evaluations. Methods Pubertal staging, anthropometric measures, PHV, skin fold thickness (SFT) and IGF-I and fasting Insulin levels were measured. Results Early maturing girls achieved similar final height compared to late maturing girls (166.1 vs 167.1 cm, p = 0.36). Early pubertal onset was associated with significantly greater PHV (8.7 vs. 7.4 cm/year, p < 0.001) and a longer puberty duration (age at onset of breast development to age at PHV [1.8 vs. 1.1 years, p < 0.001]) compared with late maturation. After correcting for age at pubertal onset, neither BMI, SFT nor IGF-I levels differed between early versus late maturing girls. By contrast, fasting insulin levels were significantly higher in early compared with late maturing girls 1.5, 2.0 and 3.0 years after pubertal onset (all p = 0.039). Conclusion Growth velocity was higher and more prolonged in early compared with late maturing girls and associated with higher insulin levels. Thus, the higher insulin levels may compensate for the shorter total growth period by intensifying the pubertal growth period.

Beyond the method change in clinical practice: evaluation of insulin-like growth factor I assay.

Insulin-like growth factor I (IGF-I) is the preferred biomarker for diagnosing and monitoring growth-related disorders but its serum quantification presents several difficulties since different IGF-I assays still leads to different IGF-I concentrations, especially when results are either above or below the normal range. We conducted a prospective study between November and December 2020 at a tertiary University Hospital with 212 serum samples to determine the analytical performance of the IGF-I assay on the Cobas e411 (Roche Diagnostics) and compare it with that of the Immulite 2000XPi (Siemens). In this work, we report for the first time the existence of discrepancies between IGF-I levels measured by Immulite 2000XPi and Cobas e411. Deming regression model provided a slope of 1.570 (95% CI: 1.395-1.745) and an intercept of-58.591 (95% CI:-89.151 to-28.030), with R2=0.967 and average bias of +53.061 with overestimation of IGF-I. It was found that Cobas e411 provides abnormally high IGF-I concentrations, but further studies are required to elucidate the cause of the discrepancies. Our data can alert clinicians and laboratory professionals of this situation and avoid misinterpretation of increased IGF-I levels as a therapeutic failure rather than as a problem associated with this method change.

P–714 Insulin-like growth factor-I as a mediator of the effect of transdermal testosterone in poor responder patients

Abstract Study question Is insulin-like growth factor-I (IGF-I) a mediator of the effect of transdermal testosterone (TT) in poor responder (PR) patients? Summary answer IGF-I might be a mediator of the effect of TT in PR patients who undergo an IVF cycle What is known already Many strategies have been tried to improve the results in PR patients. Androgen supplementation with TT is the only that has significantly increased live birth rate in these patients. The mechanism by which TT might influence on the better results remains unclear but it is likely mediated or facilitated by IGF-I. Testosterone increases the number of primordial follicles, increase IGF-I by threefold and increase IGF-I receptor mRNA by fivehold in primordial follicles in primates. Some studies have suggested that IGF-I could be a parameter that reflects the endocrinological environment of mature follicles, which is correlated with oocyte and embryonic quality Study design, size, duration This prospective cohort study of 93 women PR according Bologna criteria treated with TT and IVF/ICSI was conducted between May 2015 and December 2016 Participants/materials, setting, methods Exogenous andogenization with TT for 5 days prior to ovarian stimulation was carried out. Hormonal parameters were evaluated: basal FSH, LH and Estradiol, AMH, IGF–1 pre and post TT. Ultrasound parameterswere also analysed: antral follicle count (AFC) and number of pre-ovulatory follicles the day of HCGr. We compared these parameters according to the ovarian response: adequate (> 4 oocytes) or insufficient (<3 oocytes), as well as the pregnancy was achieved or not. Main results and the role of chance Baseline characteristics of the patients were: 36.9 years, FSH 11.8, AMH 0.86 and RFA 5.3. In 83% of the patients the oocyte retrieval was carried out, obtaining an average of 3.8 MII oocytes and 2.9 embryos of 2pn with a clinical pregnancy rate per transfer of 33.3%. The FORT Test (AFC/pre-ovulatory follicles x100) was 70%, higher than that observed in other studies with patients with PR without TT (55%). In cases in which an insufficient response was obtained (<3 oocytes) or the cycle was canceled, a higher age and FSH and lower AMH were observed (p < 0.05). There were no differences in the rest of the parameters. Evaluating the hormonal and ultrasound parameters depending on whether or not pregnancy was achieved, a significant increase in IGF1 pre and post-TT was observed in the cases of pregnancy (31.5%) compared to those cases where there was no pregnancy (10.9%) (p = 0’01). There were no differences in the rest of the parameters. A significant correlation was found between AMH, AFC and increase in IGF-I levels (p < 0’05). Limitations, reasons for caution This a prospective cohort study with limited number of patients included. Wider implications of the findings: The significant increase in serum levels of IGF–1 in pregnant patients would indicate the existence of a more favorable clinical setting for the administration of testosterone, probably related to a more favorable ovarian reserve as demonstrated by its correlation with serum levels of AMH and with the AF. Trial registration number Not applicable

THE IGF -I IN DIABETIC PATIENTS WITH RESISTANT HYPERTENSION DECREASES INSULIN RESISTANCE BUT IS ASSOCIATED WITH CARDIOVASCULAR TARGET ORGAN DAMAGE

Objective: The insulin-like growth factor-I (IGF-I) is involved in glucose metabolism and may contribute to the accelerated cardiovascular disease. The aim of the study was to assess IGF-I level in diabetic patients with resistant hypertension (RHTN) and to evaluate its association with glucose metabolism and cardiac, renal and brain tissues. Design and method: The study included 19 diabetic patients with RHTN (mean age 58.9 ± 7.6 years, five men, mean office BP (systolic/diastolic) 174.8 ± 20.7/94.6 ± 15mmHg, mean HbA1c 7 ± 0.8%) and 21 age- and sex-matched patients with RHTN without diabetes mellitus (DM). Office BP, echocardiography, kidney and brain MRI, lab tests (IGF-1, plasma glucose and insulin levels, HOMA-index, HbA1c, serum creatinine, serum cystatin, eGFR (MDRD formula) and 24 h microalbuminuria) were performed in all patients. On average, patients were taking 4.2 ± 0.8 antihypertensive drugs. Results: IGF-I level was in the normal range in 18 (95%) patients with DM+RHTN and in 100% of patients with RHTN without DM, one diabetic patient with RHTN had elevated IGF-I levels. The mean IGF-I values in hypertensive patients with DM and those without DM were the same. In diabetic patients with RHTN the IGF-I level was inversely correlated to HOMA-IR index (R = -0.87, P = 0.002), but had a direct correlation with basal glucose level (R = 0.48, P = 0.04). In addition, increase in IGF-I level was associated with both of left ventricular mass (R = 0.49, P = 0.03), and the end-diastolic interventricular septum thickness (R = 0.59, P = 0.008), with decreased renal function (R = 0.64, P = 0.003 for serum creatinine; R = 0.76, p = 0.01 for serum cystatin; R = -0.50, P = 0.03 for eGFR), microalbuminuria level (R = 0.61, P = 0.03), as well as with structural kidney damage (R = -0.67, P = 0.04 for the medulla volume according to kidney MRI) and brain damage (R = 0.89, P = 0.015 for Evans’ index as a MRI- sign of brain atrophy) Conclusions: Most diabetic patients with RHTN have a normal IGF-I level, which does not differ from that in patients with RHT without DM. Although an increase in IGF-I level is associated with a decrease in insulin resistance, our data suggest the possible participation of IGF-I in the development of myocardial hypertrophy, the progression both of chronic kidney disease and brain atrophy.

A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the Response to Traumatic Brain Injury.

In response to injury, the brain produces different neuroprotective molecules, such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by the brain from the circulation in response to physiological stimuli. Herein, we analyzed in mice the relative contribution of circulating and locally produced IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI) induced by a controlled impact resulted in increased IGF-I levels in the vicinity of the lesion, but mice with low serum IGF-I showed significantly lower increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion site after injury, and at the same time serum IGF-I levels decreased. Collectively, these data suggest that serum IGF-I enter into the brain after TBI and contributes to increased brain IGF-I levels at the injury site. This connection between central and circulating IGF-I provides an amenable route for treatment, as subcutaneous administration of IGF-I to TBI mice led to functional recovery. These latter results add further support to the use of systemic IGF-I or its mimetics for treatment of brain injuries.

Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy.

By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox ( DFX ), an oral single dose therapy, has improved the compliance to chelation.AimsTo study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX treatment in relation to ferritin level.MethodsOnly BTM patients with hepatitis negative screening (checked every year) and on treatment with DFO for at least five years and with DFX for four years were enrolled. Liver function tests including serum bilirubin, alanine transferase (ALT), aspartate transferase (AST), albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every six months in 40 patients with BTM.ResultsDFX treatment (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM; this was associated with a significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively, p < 0.05). IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels.The negative correlation between serum ferritin concentrations and ALT suggests that the impairment of hepatic function negatively affect IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis.ConclusionsSome impairment of liver function can occur in hepatitis negative thalassemic patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.

Bioavailable Insulin-like Growth Factor-I Inversely Related to Weight Gain in Postmenopausal Women Regardless of Exogenous Estrogen

Weight gain, insulin-like growth factor-I (IGF-I) levels, and excess exogenous steroid hormone use are putative cancer risk factors, yet their interconnected pathways have not been fully characterized. This cross-sectional study investigated the relationship between plasma IGF-I levels and weight gain according to body mass index (BMI), leptin levels, and exogenous estrogen use among postmenopausal women. This study included 794 postmenopausal women who enrolled in an ancillary study of the Women's Health Initiative Observational Study between February 1995 and July 1998. The relationship between IGF-I levels and weight gain was analyzed using ordinal logistic regression. We used the molar ratio of IGF-I to IGF binding protein-3 (IGF-I/IGFBP-3) or circulating IGF-I levels adjusting for IGFBP-3 as a proxy of bioavailable IGF-I. The plasma concentrations were expressed as quartiles. Among the obese group, women in the third quartile (Q3) of IGF-I and highest quartile of IGF-I/IGFBP-3 were less likely to gain weight (>3% from baseline) than were women in the first quartiles (Q1). Among the normal-weight group, women in Q2 and Q3 of IGF-I/IGFBP-3 were 70% less likely than those in Q1 to gain weight. Among current estrogen users, Q3 of IGF-I/IGFBP-3 had 0.5 times the odds of gaining weight than Q1. Bioavailable IGF-I levels were inversely related to weight gain overall. Although weight gain was not consistent with increases in IGF-I levels among postmenopausal women in this report, avoidance of weight gain as a strategy to reduce cancer risk may be recommended.

Relationship between Insulin-Like Growth Factor I Levels, Early Insulin Treatment, and Clinical Outcomes of Very Low Birth Weight Infants

Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 μg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

SIRT1 regulates adaptive response of the growth hormone--insulin-like growth factor-I axis under fasting conditions in liver

Adaptation under fasting conditions is critical for survival in animals. Sirtuin 1 (SIRT1), a protein deacetylase, plays an essential role in adaptive metabolic and endocrine responses under fasting conditions by modifying the acetylation status of various proteins. Fasting induces growth hormone (GH) resistance in the liver, leading to decreased serum insulin-like growth factor-I (IGF-I) levels as an endocrine adaptation for malnutrition; however, the underlying mechanisms of this action remain to be fully elucidated. Here we report that in vivo knockdown of SIRT1 in the liver restored the fasting-induced decrease in serum IGF-I levels and enhanced the GH-dependent increase in IGF-I levels, indicating that SIRT1 negatively regulates GH-dependent IGF-I production in the liver. In vitro analysis using hepatocytes demonstrated that SIRT1 suppresses GH-dependent IGF-I expression, accompanied by decreased tyrosine phosphorylation on signal transducer and activator of transcription (STAT) 5. GST pull-down assays revealed that SIRT1 interacts directly with STAT5. When the lysine residues adjacent to the SH2 domain of STAT5 were mutated, STAT5 acetylation decreased concomitant with a decrease in its transcriptional activity. Knockdown of SIRT1 enhanced the acetylation and GH-induced tyrosine phosphorylation of STAT5, as well as the GH-induced interaction of the GH receptor with STAT5. These data indicate that SIRT1 negatively regulates GH-induced STAT5 phosphorylation and IGF-I production via deacetylation of STAT5 in the liver. In addition, our findings explain the underlying mechanisms of GH resistance under fasting conditions, which is a known element of endocrine adaptation during fasting.

Restorative effect of intracerebroventricular insulin-like growth factor-I gene therapy on motor performance in aging rats

Insulin-like growth factor-I (IGF-I) is a powerful neuroprotective molecule in the brain and spinal cord. We have previously shown that intracerebroventricular (i.c.v.) IGF-I gene therapy is an effective strategy to increase IGF-I levels in the cerebrospinal fluid (CSF). Since aging in rats is associated with severe motor function deterioration, we implemented i.c.v. IGF-I gene therapy in very old rats (30–31 months) and assessed the beneficial impact on motor performance. We used recombinant adenovectors (RAds) expressing either green fluorescent protein (GFP) or rat IGF-I. Injection in the lateral or fourth ventricle led to high transgene expression in the ependymal cell layer in the brain and cervical spinal cord. RAd-IGF-I-injected rats but not RAd-GFP-injected controls, showed significantly increased levels of CSF IGF-I. Motor tests showed the expected age-related decline in aged rats. Seventeen-day IGF-I gene therapy induced a significant improvement in motor performance in the aged but not in the young animals. These results show that IGF-I is an effective restorative molecule in the aging brain and spinal cord. The data also reveal that the ependymal route constitutes a promising approach for implementing protective IGF-I gene therapy in the aging CNS.

Pregnancy-induced increase in circulating IGF-I is associated with progression of diabetic retinopathy in women with type 1 diabetes

Objective To evaluate the influence of Insulin-like Growth factor-I (IGF-I) and Placental Growth Hormone (GH) on progression of diabetic retinopathy during pregnancy in women with type 1 diabetes. Design Observational study of 88 consecutive pregnant women with type 1 diabetes for median 16.5 years (range 1–36) and HbA 1c 6.6% (5.2–10.5) in early pregnancy. At 8, 14, 21, 27 and 33 weeks blood samples were drawn for measurement of IGF-I, placental GH and Hemoglobin A 1c (HbA 1c) and blood pressure was recorded. Fundus photography was performed at 8 and 27 weeks. Diabetic retinopathy was classified in five stages. Progression was defined as deterioration of at least one stage of diabetic retinopathy and/or development of macular edema on at least one eye. Results Placental GH and IGF-I levels increased throughout pregnancy and new onset or progression of diabetic retinopathy occurred in 22 (25%). A steeper increase in women with progression of diabetic retinopathy resulted in higher IGF-I levels at 27 weeks ( p = 0.01) and 16% higher IGF-I levels throughout pregnancy ( p = 0.02) compared with women without progression while similar levels of placental GH ( p = 0.58) and HbA 1c ( p = 0.85) were observed throughout pregnancy. In a multivariate logistic regression analysis, progression of diabetic retinopathy was associated with higher IGF-I levels at 33 weeks (odds ratio 2.0 [95% confidence interval 1.1–3.6], p = 0.02) and higher systolic blood pressure at 8 weeks (1.9 [1.1–3.2], p = 0.02) independent of placental GH and HbA 1c levels. Conclusions Pregnancy-induced increase in IGF-I levels is associated with progression of diabetic retinopathy in women with type 1 diabetes.

Selected Metabolic and Hormonal Profiles during Maintenance of Spontaneous Ovarian Cysts in Dairy Cows

Information is lacking regarding the relationship between metabolic and hormonal profiles and the maintenance of spontaneous ovarian cyst disease in dairy cows. For this reason, the concentrations of non-esterified fatty acids (NEFA), insulin-like growth factor I (IGF-I) and cortisol (C) were investigated during the spontaneous course of ovarian cyst disease in dairy cows (n=6) between the 7th and 16th weeks post-partum (PP). The control group consisted of normally cycling cows (n=6). Blood samples were collected twice a day, and plasma was analysed using different techniques. Progesterone and 15-ketodihydro-PGF(2α) plasma profiles were investigated to confirm the ovulatory or anovulatory conditions of the cows. Cortisol plasma levels were not significantly different among sampling times within each group or between the two groups. NEFA plasma levels were significantly higher in cycling cows compared to cystic cows at the 16th week PP (p<0.01), but with rather low values, indicating by now sparse mobilization of fat stores. Insulin-like growth factor I plasma concentrations were higher in cystic cows during the 8th, 10th, 11th (p<0.01) and 16th week PP (p<0.05), indicating that the presence of ovarian cysts coincides with increased IGF-I levels. These results suggest no influence of cortisol and NEFA levels in cysts maintenance, while a possible involvement of IGF-I can be suspected not only in the pathogenesis, as already known, but also in the maintenance of spontaneous cystic ovarian disease in cattle.

Sustained low‐dose growth hormone therapy optimizes bioactive insulin‐like growth factor‐I level and may enhance CD4 T‐cell number in HIV infection

High-dose recombinant human growth hormone (rhGH) (2-6 mg/day) regimes may facilitate T-cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose rhGH regimens increase insulin-like growth factor-I (IGF-I) to supra-physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T-cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.e., free) IGF-I. A previous 16-week pilot-study included six HIV-infected patients on stable HAART to receive rhGH 0.7 mg/day, which increased total (+117%, P < 0.01) and free (+155%, P < 0.01) IGF-I levels. The study was extended to examine whether continuous use of low-dose rhGH (0.7 mg/day until week 60; 0.4 mg/day from week 60 to week 140) would maintain expedient IGF-I levels and improve CD4 T-cell response. Total and free IGF-I increased at week 36 (+97%, P < 0.01 and +125%, P < 0.01, respectively) and week 60 (+77%, P = 0.01 and +125%, P < 0.01) compared to baseline levels (161 +/- 15 and 0.75 +/- 0.11 microg/L). CD4 T-cell number increased at week 36 (+15%, P < 0.05) and week 60 (+31%, P = 0.01) compared to baseline levels (456 +/- 55 cells/microL). Following rhGH dose reduction, total IGF-I and CD4 T-cell number remained increased at week 88 (+44%, P = 0.01 and +33%, P < 0.01) and week 140 (+46%, P = 0.07 and +36%, P = 0.02) compared to baseline levels. These data support the notion that low-dose rhGH regimens may increase expediently total and bioactive IGF-I and improve T-cell restoration in patients infected with HIV on HAART.

Changes in Endothelial Dysfunction and Associated Cardiovascular Disease Morbidity Markers in GH-IGF Axis Pathology

Arterial endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes individuals to the deposition of unstable atherosclerotic plaques. It can also lead to increased arterial stiffness, which is an accepted cause of increased arterial pulse wave velocity (APWV). Endothelial dysfunction is reversed by recombinant human growth hormone (rhGH) therapy in patients with growth hormone (GH) deficiency (GHD), favorably influencing the risk for atherogenesis. Endogenous human growth hormone (hGH), secreted by the anterior pituitary, and levels of insulin-like growth factor-I (IGF-I), produced in response to hGH stimulation of the liver, peak during early adulthood, but decline throughout adulthood. It is suspected that low-grade inflammatory cardiovascular pathophysiologic markers such as homocysteine, nitric oxide, C-reactive protein (CRP), and fibrinogen and plasminogen activator inhibitor along with changes in lipid and glucose metabolism may all contribute to GHD-associated metabolic and cardiovascular complications. These effects are associated with increased APWV, but are attenuated by rhGH therapy in GHD. GH replacement increases IGF-I levels and reduces CRP and large-artery stiffness. Reviews of rhGH in the somatopause have not been overtly favorable. Whereas reviews of rhGH/rhIGF-I combinations in GH resistance are more positive than those for rhGH alone, their combined use in the somatopause is limited. Senescent individuals may benefit from such a combination.

Measurement of insulin-like growth factor I (IGF-I) in normal adults, patients with liver cirrhosis and acromegaly: experience with a new competitive enzyme immunoassay.

A competitive enzyme immunoassay for the determination of human insulin-like growth factor I in microtiter plates was established. Using a polyclonal antiserum raised in rabbits against hIGF-I ovalbumin conjugate the assay system was able to detect IGF-I at a range of 12-800 pg/well with a sensitivity of 10 pg/well. It showed a low (< 0.5%) cross reactivity with hIGF-II. The serum concentrations of IGF-I found by EIA agreed well with those found in a conventional RIA (r = 0.965, p < 0.001). Effects of age and sex on IGF-I levels were studied in 260 normal adults. There was no evidence for sex differences but a steep decline of values from the third to the fourth and from the eight to the ninth decade, respectively. To asses the diagnostic capability of the IGF-I determination in liver cirrhosis, 71 sera of patients classified according to Child classes (A-C) were measured. Although significantly diminished concentrations were found in class B vs A and in class C vs B, the diagnostic sensitivity in cross-sectional examinations proved to be low (class A: 0.33, class B: 0.67). Only in the case of extensively destroyed liver parenchyma (Child C: 0.94) IGF-I was a good indicator of impaired hepatocellular capacity. In 29 patients with acromegaly serum IGF-I levels were investigated. All patients with active acromegaly showed increased IGF-I levels. In contrast, in inactive or weakly active acromegaly values were considerably lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the plasma levels of insulin-like growth factor-I from the onset of spawning migration through upstream migration in chum salmon

An increase in activity of the pituitary–gonadal axis (PG-axis) and gonadal development are essential for the onset of spawning migration of chum salmon from the Bering Sea. In the Bering Sea, fish with larger body sizes initiated gonadal development and commenced spawning migration to the natal river by the end of summer. We thus hypothesized that insulin-like growth factor-I (IGF-I), a somatotropic signal that interacts with the PG-axis, can be one of such factors responsible for the onset of migration, and examined changes in plasma levels and hepatic expression of IGF-I gene in oceanic and homing chum salmon in 2001–2003. The plasma IGF-I levels and corresponding body sizes in maturing adults, which had developing gonads, were significantly higher than those in immature fish in all years examined. Such increase in the plasma IGF-I levels in maturing fish was observed even in the Gulf of Alaska during February 2006, while coincident increase was not observed in the hepatic amounts of IGF-I mRNA. In autumn, the plasma IGF-I levels in homing adults decreased during upstream migration in the Ishikari River-Ishikari bay water system in Hokkaido, Japan. In conclusion, the plasma IGF-I levels increased with gonadal development when chum salmon migrated from the winter Gulf of Alaska to the summer Bering Sea. Circulating IGF-I may interact with the PG-axis and promote gonadal development that is inseparable from the onset of spawning migration. Circulating IGF-I levels were thereafter lowered in accordance with final maturation during upstream migration in the breeding season.

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.

Acromégalie

Acromegaly is a rare disease usually caused by growth hormone (GH) hypersecretion, due to a pituitary adenoma; in very rare cases, acromegaly is due to ectopic secretion of GHRH, responsible for pituitary hyperplasia. Owing to its insidious onset, acromegaly is often diagnosed late (4 to > 10 years after onset), at an average age of about 40 years, in front of an acquired, slowly progressing disfigurement mainly involving the face and extremities. Acromegaly has also rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. The diagnosis is based on an increased serum GH concentration unsuppressed following an oral glucose load (oral glucose tolerance test -OGTT-) and an increased insulin-like growth factor-I (IGF-I); according to a 2000 Consensus statement, if the basal serum GH is above 0,4microg/L (1.2mIU/L) and/or if the IGF-I is elevated, an OGTT must be performed. If the lowest GH value (nadir) during OGTT remains above 1microg/L (3mIU/L), acromegaly is confirmed. With the generalized use of very sensitive assays nowadays, it has recently been considered that this cutoff should be decreased to 0,3microg/L (0.9mIU/L). Treatment is aimed at correcting (or preventing) tumor compression by excising the culprit lesion, and at reducing GH and IGF-I levels to normal values (or at least to a "safe" GH level of < 2microg/L or < 6mIU/L). A stepwise therapeutic strategy is used: transsphenoidal surgery is often the first-line treatment; when surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used, somatostatin analogs being generally preferred; the GH antagonist (pegvisomant) is used in patients that are resistant or intolerant to somatostatin analogs. Prognosis of acromegaly has improved in the recent years: adequate hormonal disease control is achieved in most cases, allowing life expectancy similar to that of the general population.

Early Elective Insulin Therapy Can Reduce Hyperglycemia and Increase Insulin-Like Growth Factor-I Levels in Very Low Birth Weight Infants

To investigate the use of insulin throughout the first week of life in very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the dominant hormone involved in fetal growth, and low levels have been implicated in neonatal morbidities, such as retinopathy of prematurity. In this pilot randomized controlled study (n = 16), the intervention group received insulin (0.025 U/kg/hr) on days 1 to 7, with 20% dextrose to maintain normoglycemia. Control infants received standard neonatal care. All infants received continuous glucose monitoring. The intervention and standard care groups had similar mean gestational age (+/- standard deviation), 26.2 (+/- 2.5) vs 26.9 (+/- 2.7) weeks, and birth weight, 0.79 (+/- 0.26) vs 0.73 (+/- 0.16) kg. The standard care infants were hyperglycemic (sensor glucose >10 mmol/L [180 mg/dL]) for 35.9% of the study period, compared with 7.6% for the insulin-treated infants (P = .035). The duration of time with hypoglycemia (<2.6 mmol/L [47 mg/dL]) did not differ between the 2 groups (P = .746). The insulin-treated group had a 2.4-fold increase in mean IGF-I bioactivity (P = .005). Early insulin therapy improves blood glucose control and increases IGF-I bioactivity levels. This could result in less morbidity associated with hyperglycemia and reduced IGF-I levels.

RETRACTED: Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I, thereby reducing reperfusion-induced apoptosis in mice

Calcitonin gene-related peptide (CGRP) increases insulin-like growth factor-I (IGF-I) production in fetal rat osteoblasts in vitro, suggesting that stimulation of sensory neurons might increase IGF-I production, thereby preventing apoptosis. We examined whether stimulation of sensory neurons by capsaicin might reduce reperfusion-induced hepatic apoptosis by increasing IGF-I production. Administration of capsaicin increased tissue levels of IGF-I and IGF-I mRNA in various organs in wild-type (WT) mice, but not in CGRP-knock-out (CGRP-/-) mice. Administration of CGRP increased tissue levels of IGF-I and IGF-I mRNA in both WT and CGRP-/- mice. Increases in hepatic tissue levels of TNF, serum levels of transaminases, hepatic apoptosis and hepatic tissue levels of caspase-3 after hepatic ischemia/reperfusion (I/R) were more marked in CGRP-/- mice than in WT mice. Hepatic IGF-I levels were increased in WT mice after reperfusion, while they were not changed in CGRP-/- mice. Although administration of capsaicin enhanced increases in IGF-I levels and reduced reperfusion-induced events in WT mice, it had no effect in CGRP-/- mice. Administration of CGRP and IGF-I reduced reperfusion-induced effects in both strains of mice. These observations suggested that capsaicin-induced sensory neuron activation, which leads to release of CGRP, might increase IGF-I production, thereby reducing reperfusion-induced liver injury by reducing apoptosis.