Insulin Growth Factor-1 Levels Research Articles

Serum Insulin-Like Growth Factor-1 and Nitric Oxide Levels in Parkinson's Disease

The aim of this study was to investigate the role of circulating growth hormone (GH), insulin growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and nitric oxide (NO) concentrations in the patients suffering from Parkinson's disease (PD). The study groups were consisted of 25 patients with PD and 25 matched healthy subjects as a control. The NO level of patients in PD group (2.3 ± 0.4 μmol/L) was significantly lower than that in the control group (2.8 ± 0.6 μmol/L) (P:.011). Although there were no statistically significant differences in the GH, IGF-1, and IGF BP-3 levels among the two groups, in this preliminary study, we found low NO and mildly elevated IGF-1 levels in the patients with PD. The results may be associated with adaptation or protective mechanisms in the neurodegenerative disease processes such as seen in the PD. Further studies should be carried out to confirm our results.

Study Protocol: insulin and its role in cancer

BackgroundStudies have shown that metabolic syndrome and its consequent biochemical derangements in the various phases of diabetes may contribute to carcinogenesis. A part of this carcinogenic effect could be attributed to hyperinsulinism. High levels of insulin decrease the production of IGF-1 binding proteins and hence increase levels of free IGF-1. It is well established that bioactivity of free insulin growth factor 1 (IGF-1) increases tumor turnover rate. The objective is to investigate the role of insulin resistance/sensitivity in carcinogenesis by studying the relation between insulin resistance/sensitivity and IGF-1 levels in cancer patients. We postulate that hyperinsulinaemia which prevails during initial phases of insulin resistance (condition prior to overt diabetes) increases bioactivity of free IGF-1, which may contribute to process of carcinogenesis.Methods/DesignBased on our pilot study results and power analysis of the same, we have designed a two group case-control study. 800 proven untreated cancer patients (solid epithelial cell tumors) under age of 50 shall be recruited with 200 healthy subjects serving as controls. Insulin resistance/sensitivity and free IGF-1 levels shall be determined in all subjects. Association between the two parameters shall be tested using suitable statistical methods.DiscussionWell controlled studies in humans are essential to study the link between insulin resistance, hyperinsulinaemia, IGF-1 and carcinogenesis. This study could provide insights to the role of insulin, insulin resistance, IGF-1 in carcinogenesis although a precise role and the extent of influence cannot be determined. In future, cancer prevention and treatment strategies could revolve around insulin and insulin resistance.

The acute effects of different whole body vibration amplitudes on the endocrine system of young healthy men: a preliminary study

Whole body vibration (WBV) has been suggested as an alternative form of exercise producing adaptive responses similar to that of resistance training. Very limited information is available on the effects of different vibration parameters on anabolic hormones. In this study, we compared the acute effects of different WBV amplitudes on serum testosterone (T) and insulin growth factor-1 (IGF-1). Nine healthy young recreationally active adult males (age 22 +/- 2 years, height 181 +/- 6.3 cm, weight 77.4 +/- 9.5 kg) voluntarily participated in this randomized controlled (cross-over design) study. The subjects performed 20 sets of 1 min each of WBV exercise in the following conditions: Non-vibration condition (control), low amplitude vibration [low (30 Hz, 1.5 mm peak-to-peak amplitude)] and high amplitude vibration [high (30 Hz, 3 mm peak-to-peak amplitude)]. Blood samples were collected before, after 10 sets, at the end (20th set) and after 24 h of the exercise bout. WBV exercise did not produce significant changes in serum T and IGF-1 either with low or high amplitude when compared with the control condition. The results of this study demonstrate that a single session of WBV exposure with a frequency of 30 Hz and amplitudes of 1.5 and 3 mm does not noticeably alter serum T and IGF-1 levels.

Cathepsin S Controls Angiogenesis and Tumor Growth via Matrix-derived Angiogenic Factors

The cysteine protease cathepsin S is highly expressed in malignant tissues. By using a mouse model of multistage murine pancreatic islet cell carcinogenesis in which cysteine cathepsin activity has been functionally implicated, we demonstrated that selective cathepsin S deficiency impaired angiogenesis and tumor cell proliferation, thereby impairing angiogenic islet formation and the growth of solid tumors, whereas the absence of its endogenous inhibitor cystatin C resulted in opposite phenotypes. Although mitogenic vascular endothelial growth factor, transforming growth factor-beta1, and the anti-angiogenic endostatin levels in either serum or carcinoma tissue extracts did not change in cathepsin S- or cystatin C-null mice, tumor tissue basic fibroblast growth factor and serum type 1 insulin growth factor levels were higher in cystatin C-null mice, and serum type 1 insulin growth factor levels were also increased in cathepsin S-null mice. Furthermore, cathepsin S affected the production of type IV collagen-derived anti-angiogenic peptides and the generation of bioactive pro-angiogenic gamma2 fragments from laminin-5, revealing a functional role for cathepsin S in angiogenesis and neoplastic progression.

Individualized therapy for growth hormone deficiency

The use of human growth hormone to treat children with short stature resulting from growth hormone deficiency or insufficiency has now accrued over 40 years of clinical experience with a satisfactory safety and efficacy record. Growth hormone deficiency is the primary indication for growth hormone treatment in childhood. It is basically a clinical diagnosis, based upon auxologic features, and confirmed by biochemical testing. For assurance of compliance, dosing and, perhaps, safety considerations, a dosing algorithm based upon insulin-like growth factor-I response seems to be appropriate. Current data suggest that such algorithms reflect the true growth hormone needs of a patient, and allow optimization of growth hormone treatment. For patients who display a suboptimal growth response or in whom the insulin growth factor levels remain low with assurance of adherence to the injection schedule, it is reasonable to increase the growth hormone dose. The availability of recombinant human insulin-like growth factor-I treatment may provide an alternative for massively increasing the dose of growth hormone. Dose reductions should be considered for patients with serum insulin-like growth factor-I levels substantially above the normal range.

Insulin Growth Factor-1 (IGF-1) and Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) in PCOS IVF Patients: Correlations With Outcome

Protocols incorporating OCP/GnRH-agonist dual suppression followed by low-dose gonadotropin therapy are commonly utilized to induce ovulation for IVF in PCOS patients. Follicular recruitment in PCOS patients demonstrates that IGF-1 and IGFBP-3 are predictive of ovarian response. The purpose of this study was to observe IGF-1 and IGFBP-3 levels during the course of dual suppression/ low dose gonadotropin stimulation in PCOS patients and evaluate their value as predictive factors for IVF outcome. Prospective analysis of serial serum levels of IGF-1 and IGFBP-3 from PCOS patients undergoing IVF Serum was prospectively collected and cryopreserved for analysis at a later date from PCOS patients cycles (n=77) undergoing IVF with the dual suppression /low dose gonadotropin protocol over a two year period. Twenty patients (29.0%) were concurrently treated with metformin. Growth Hormone was not used. Serum IGF-1 and IGFBP-3 levels were measured by ELISAs (R&D Systems, MN) on day 3 of GnRH-agonist withdrawal bleed and on the day of hCG administration. Statistical analysis included non-parametric and Chi-Square tests. The mean age of patients was 30.6±2.9 years, and the mean BMI was 24.1±4.7. Peak mean estradiol levels were 1578 ± 912 pg/mL on day of hCG. An average of 13.3±3 oocytes with 9.7±4.9 mature oocytes were retrieved per cycle, with 6.9±3.8 normally fertilized oocytes per cycle. Clinical and ongoing pregnancy rates were 58.5% and 50.9%, respectively. IGF-1 and IGFBP-3 levels increased during stimulation (IGF-1, 187.4±78.1ng/mL vs. 243.5±146.0[day 3 vs. day of hCG], p<.0001; IGFBP-3, 1204.2±897.0 ng/mL vs. 1710.8±1532.5,[day 3 vs. day of hCG], p<.002). Metformin treatment did not significantly affect day 3 or day of hCG levels of IGF-1 or IGFBP-3, or the significant trend of increasing levels of IGF-1 and IGFBP-3 during stimulation. Those patients who had a decrease in IGF-1 levels from day 3 to day of hCG had higher mean numbers of oocytes retrieved (15.6±7.6 vs. 11.5±4.9, p=.02). However, patients whose IGF-1 levels fell during stimulation also had a significant increase in the number of immature oocytes; consequently, those whose IGF-1 levels rose had a higher percentage of mature oocytes (79.8% vs. 62.5% mature oocytes, rise vs. fall of IGF1 day 3 to day of hCG, p= 0.02). An increase in IGFBP-3 levels during stimulation was associated with a greater likelihood of becoming pregnant (IGFBP-3, p=.03) and of ongoing pregnancy (IGFBP-3, p=.02). For the first time we report on the dynamic changes of IGF-1 and IGFBP-3 during ovarian hyperstimulation for PCOS IVF patients. In this patient population we found a mean increase in levels of IGF-1 and IGFBP-3 during stimulation. Increasing levels of IGF-1 were associated with a higher percentage of mature oocytes, suggesting its higher bioavailability to maturing follicles. Increasing levels of IGFBP-3 during stimulation were associated with a higher likelihood of pregnancy and ongoing pregnancy. It is possible that this stimulation protocol creates a unique intraovarian environment affecting the important regulatory roles that IGF-1 and IGFBP-3 play in follicular recruitment and maturation. Interestingly, in this setting treatment with an insulin sensitizing agent did not affect ovarian responsiveness. Future studies into the Growth hormone/IGF-1 axis in the intraovarian environment during suppression and stimulation for IVF are needed.

Relationship between Insulin-Like Growth Factor 1 and Bone Mineral Density in Men Aged over 65 Years

Objective: To determine the association between insulin growth factor 1 (IGF-1) and bone mineral density (BMD) in men over 65 years of age. Subjects and Methods: Forty-one male patients aged 65–88 years without a history of drug use or illness which is known to affect BMD were enrolled in the study. The control group consisted of 20 healthy men (19–62 years old). An immunoradiometric assay was used to measure IGF-1 levels. Dual-energy X-ray absorptiometry was used to determine BMD at the proximal femur and lumbar spine. A detailed questionnaire was used to assess the epidemiological findings. Results: The men over 65 years of age had a lower mean IGF-1 level (102.04 ± 36.65 vs. 196.62 ± 84.86 ng/ml) and a lower mean BMD at the femoral neck, trochanter and intertrochanteric zones, Ward’s triangle and total hip than the controls. No statistically significant association was observed in the BMD of the lumbar vertebrae between the patients and controls. IGF-1 levels were strongly and negatively correlated with age (p < 0.0001, r = –0.82). Logistic regression analysis showed that low IGF-1 levels were strongly associated with osteopenia of the total hip, femoral neck, trochanter and intertrochanteric zone. Conclusion: The finding shows that low serum IGF-1 levels were associated with an increased risk of hip osteopenia and, hence, at least partly responsible for the osteopenia observed in men aged 65 years or over.

Osteoporosis: Prevention and treatment in anorexia nervosa

One of the most serious and potentially permanently disabling medical complications of anorexia nervosa is osteoporosis, which greatly increases the long-term risk of bone fractures. The decreased bone density in patients with anorexia nervosa (AN) is due to the many effects on bone metabolism of amenorrhea, reduced levels of insulin growth factor-1 (IGF-1), high cortisol levels and weight loss. Although estrogen replacement therapy is clearly efficacious in preventing postmenopausal osteoporosis, its efficacy in AN is uncertain. Clinicians caring for patients with AN need to be aware of this because, despite such therapy, there may be an inexorable decline in bone mineral density in what is a relatively young group of patients. AN frequently has its onset during adolescence, when peak bone mass is normally reached, and an anorectic episode in youth may permanently impair skeletal integrity and lead to debilitating fractures and pain. It is important to recognise this formidable risk, counsel AN patients about the longterm and possibly permanent sequelae of low body weight, use densitometry to screen for bone loss and treat it accordingly. The most effective treatment is still early weight restoration and the resumption of menses.

Elevated intraocular levels of insulin-like growth factor I in a diabetic patient with acromegaly

Growth factors have become increasingly associated with various events of vitreoretinal disease. In the presence of proliferative retinopathy, elevated levels of insulin growth factor I (IGF-I) have been demonstrated in the vitreous. IGF-I expression itself is regulated by growth hormone, a hormone that is involved in the pathogenesis of acromegaly. In the present paper we report on the detection of very high IGF-levels in the subretinal fluid of a patient with acromegaly who was operated for retinal detachment. With a very sensitive RIA assay we found a four-fold elevation of the serum levels of IGF-I (604 ng/ml) and a high level of IGF-1 in the subretinal fluid (13 ng/ml). It is concluded that acromegaly may lead to an overexpression of IGF-I not only seen as increased concentrations in serum and vitreous, but in the subretinal space as well. This study emphasizes the need for further investigation of growth factor presence in pathological cavities, such as the subretinal space during retinal detachments.

Síndrome de Prader-Willi. Tratamiento con hormona de crecimiento en dos casos: Report of two cases

Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by the absence or abnormal inactivation of a critical region of the paternal chromosome 15. Clinical manifestations include marked hypotonia at birth, progressive obesity that starts during the second year of life, stunting, hypogonadism and some dysmorphic features. Some of the symptoms and signs can be explained by growth hormone (GH) deficiency. We report two females aged 12 and 13 years old with PWS. Both were very short and obese, showed blunted GH responses to provocative stimuli and had low plasma levels of Insulin Growth Factor-1 (IGF-1). They have been on GH treatment for more than two years, demonstrating a marked growth acceleration, reduction in their fat mass, improvement of their muscular strength and an increase in their IGF-1 levels.

Acute response of IGF-I and IGF binding proteins induced by thermal injury.

Previous studies demonstrate that thermal injury decreases circulating levels of insulin growth factor I (IGF-I) and alters the plasma concentration of several IGF binding proteins (IGFBP), but the mechanisms for these alterations have not been elucidated. In the current study, a 30% total body surface area full-thickness scald burn was produced in anesthetized rats, and animals were studied 24 h later. The plasma concentration of both total and free IGF-I was decreased (38 and 65%, respectively) in burn rats compared with values from time-matched control animals. Thermal injury decreased the IGF-I peptide content in liver approximately 40%, as well as in fast-twitch skeletal muscle (56-69%) and heart (28%). In contrast, IGF-I content in kidney was elevated by 36% in burn rats. Northern blot analysis of liver indicated that burn decreased the expression of small (1.7- and 0.9- to 1.2-kb) IGF-I mRNA transcripts but increased the expression of the 7.5-kb transcript. In contrast, there was a coordinate decrease in all IGF-I mRNA transcripts in muscle and kidney of approximately 30%. For liver, muscle, and kidney, there was no significant difference in the expression of growth hormone receptor mRNA between control and burn rats. Thermal injury increased plasma IGFBP-1 levels, and this change was associated with increased IGFBP-1 mRNA in both liver and kidney. IGFBP-3 levels in plasma were concomitantly decreased by burn injury. This change was associated with a reduction in IGFBP-3 mRNA in liver but an increased expression of IGFBP-3 in kidney and muscle. Thermal injury also decreased the concentration of the acid-labile subunit (ALS) in plasma and ALS mRNA expression in liver. Finally, hepatic expression of IGFBP-related peptide-1 was increased twofold in liver but was unchanged in kidney or muscle of burn rats. These results characterize burn-induced changes in various components of the IGF system in select tissues and thereby provide potential mechanisms for alterations in the circulating IGF system and for changes in tissue metabolism.

Changes in body composition, and endocrine and metabolic functions in healthy elderly Chinese men following growth hormone therapy

Background An age-related decline in growth hormone (GH) level has been established, and this decline is associated with changes in body composition as well as a general increase in susceptibility to illness and a reduced sense of well-being. The current study, a first in Asia, sought to examine the effects of GH therapy on body composition and other endocrine and metabolic functions in a group of healthy elderly Chinese men.Methods A total of 23 healthy elderly Chinese men, aged between 60 and 69 years, were injected subcutaneously, three times weekly, with 0.08 U/kg of recombinant GH for 6 months. Various hormones and biochemical parameters, together with percentage lean body mass and body fat, were measured before, 3 and 6 months after the start and 3 months after the cessation of GH therapy.Results A significant increase in lean body mass, up to 9.1% over baseline values at 3 months post-therapy, and a significant decrease in body fat, up to 3.1%, were noted. GH therapy also induced variable and significant increases in levels of insulin growth factor (IGF-I), dehydroepiandrosterone sulfate (DHEAS), insulin, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and triglyceride and significant reductions in glucose and sex hormone binding globulin (SHBG) levels. No changes in testosterone, free androgen index and cholesterol were noted. A significant and independent correlation was noted between IGF-I and insulin, TSH, DHEAS, glucose and triglyceride levels.Conclusions GH augmentation therapy was effective in improving the body composition of a group of elderly Chinese men. GH-induced positive changes in body composition in the elderly were probably a result of the direct effect of the GH. It is also possible that some of the changes were mediated through GH-induced changes in thyroid hormones, insulin, glucose, triglyceride and DHEAS. However, the mechanism of GH- induced changes in body composition remains to be defined.

Kt/V, Nutritional Parameters, Serum Cortisol, and Insulin Growth Factor-1 Levels and Patient Outcome in Hemodialysis

Despite many technical advances in dialysis care, morbidity and mortality in chronic hemodialysis patients in the United States remains high. In this study, we analyzed the effects of Kt/V, nutritional parameters (serum albumin level, triceps skin-fold thickness, mid-arm muscle circumference, and normalized protein catabolic rate), and predialysis serum cortisol and insulin growth factor-1 levels on predicting morbidity and mortality. The cohort studied consisted of 52 patients recruited from a single outpatient dialysis facility. Cox proportional hazards modeling indicated that only Kt/V predicted subsequent mortality (P = 0.02), while both predialysis cortisol levels (P = 0.03) and Kt/V (P = 0.03) predicted hospitalization. Kaplan-Meier analysis demonstrated that the ability of cortisol levels to predict hospitalization was largely confined to the group with values greater than 22 micrograms/dL predialysis. High serum cortisol levels were correlated with low serum albumin levels and a trend toward low triceps skin-fold thickness and higher normalized protein catabolic rate, suggesting a catabolic state. Both predialysis serum cortisol and insulin growth factor-1 levels were higher than those in age- and sex-matched normal human controls. These results demonstrate the importance role of Kt/V in predicting subsequent hospitalization rates and mortality, and that high predialysis serum cortisol levels correlate with a high hospitalization rate.

Insulin response to oral glucose in essential hypertensives with increased circulating levels of insulin growth factor I

Insulin response to oral glucose in essential hypertensives with increased circulating levels of insulin growth factor I

Insulin response to oral glucose in essential hypertensives with increased circulating levels of insulin growth factor I

Insulin response to oral glucose in essential hypertensives with increased circulating levels of insulin growth factor I

Subcutaneous treatment with growth hormone-releasing hormone for short stature.

In the present study we report the effects of therapy with growth hormone-releasing factor (1-29)NH2 (GRF) on growth rate, plasma levels of insulin growth factor I (IGF-I) and growth hormone (GH) secretion in 11 children who were selected solely on the basis of their short stature and normal GH secretion on standard provocative tests. All children received GRF for 6 months (5 micrograms/kg body weight subcutaneously) each evening. The 24-hour GH secretory profile was studied before and after 6 months of treatment. Simultaneously, GH secretory responses to single intravenous bolus GRF (1.5 micrograms/kg body weight) were also studied before, during, and 6 months off therapy with GRF(1-29)NH2. Plasma levels of IGF-I were measured before, during (1, 2 and 6 months), and after 6 months off therapy with GRF. Statural growth was measured at 3-month intervals. The peak plasma GH level in response to GRF was 56.04 +/- (SD) 24.46 ng/ml before treatment, and similar results were found after therapy. The 24-hour GH secretory profile did not show differences before, during, and after treatment. Comparably, no differences were found in GH pulse frequency, pulse amplitude, pulse height, pulse increment, pulse area and total area before, and 6 months off therapy with GRF. The increments in serum IGF-I achieved were not significantly different at all intervals studied. All patients increased growth velocities (mean +/- SD, cm/year) in response to GRF therapy. Our results demonstrate that GRF administration was effective in accelerating growth velocity in 11 children without GH deficiency.