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

Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

IGF-I in major depression and antidepressant treatment response

We analyzed insulin-like growth factor I (IGF-I) in serum of 78 inpatients with depression and 92 healthy controls. Patients were selected according to remission status after 6 weeks of antidepressant treatment with remission defined by Hamilton depression rating scale (HAM-D) 21-item score <10 (39 remitters and 39 non-remitters).IGF-I was analyzed in patients at admission and after 6 weeks of psychopharmacological treatment. IGF-I levels were compared between patients and controls and between remitters and non-remitters with general linear model using age, gender, and body mass index as covariates.In patients, IGF-I levels were significantly higher at admission (p=3.29E−04) and in week 6 (p=0.002) compared to controls. Furthermore, non-remitters showed significantly higher IGF-I levels at admission (p=0.046) and a trend for higher IGF-I levels in week 6 (p=0.11) compared to remitters. In remitters change in IGF-I levels during treatment was significantly correlated with change in cortisol levels (p=0.019).A genetic association analysis of polymorphisms in 10 genes contributing to the IGF-I system (IGF1, IGF1R, IGFBP1 to IGFBP7, and IGFBPL1) in the currently largest genetic databases for major depression (Psychiatric Genomics Consortium) revealed nominal associations with susceptibility for depression and treatment response, although results did not remain significant after multiple testing correction.In our study, elevated IGF-I levels were significantly associated with depression and impaired treatment response. Based on these findings IGF-I signaling could play a role in the pathophysiology of depression and could possibly influence the response to antidepressant treatment.

Maternal insulin-like growth factor-I levels (IGF-I) reflect placental mass and neonatal fat mass

Objective This study was undertaken to test the null hypothesis that serial changes in maternal insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding-protein-1 (IGFBP-1) levels during pregnancy do not reflect differences in either corrected birth weight or placental mass at term. Study design Serial blood samples were obtained before pregnancy and at 8, 16, 24, 32, and 38 weeks from 56 healthy women enrolled in various exercise training regimens. Maternal, placental, and fetal morphometric parameters were monitored throughout. Enzyme-linking immunosorbent assays were used to determine IGF-I and IGFBP-1 levels. Results IGF-I and IGFBP-1 levels varied widely among the subjects at all time points, but there was a consistent fall in IGF-I levels in early pregnancy, followed by a rapid increase between 16 and 36 weeks' gestation, whereas IGFBP-1 levels rose in the first 16 weeks and were unchanged thereafter. The strongest linear correlations with morphometric outcome were between the increase in maternal IGF-I levels from 16 to 32 weeks and corrected birth weight ( r 2 = 0.27), neonatal fat mass ( r 2 = 0.65), and placental mass at term ( r 2 = 0.50). These were improved when maternal glucose level was included in a stepwise regression analysis ( r 2 = 0.50-0.70). Conclusion There is a robust relationship among the rate of increase in individual maternal IGF-I levels after 16 weeks, placental mass, and neonatal fat mass. This does not imply causality but does indicate that midpregnancy changes in IGF-I levels may be a valuable marker for anomalous fetal growth.

Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.

Development and validation of a radioimmunoassay for fish insulin-like growth factor I (IGF-I) and the effect of aquaculture related stressors on circulating IGF-I levels

This paper describes the development and validation of a commercially available radioimmunoassay (RIA) for the detection of fish insulin-like growth factor-I (IGF-I). The assay was developed using recombinant barramundi IGF-I as antigen and recombinant tuna IGF-I as radiolabelled tracer and standard. Assay sensitivity was 0.15 ng/ml, inter-assay variation was 16% ( n=9) and intra-assay variation was 3% ( n=10). Cross reactivity of less than 0.01% was found with salmon insulin, salmon IGF-II and barramundi IGF-II, less than 0.5% with human IGF-I and less than 1% with human IGF-II. Parallel dose-response inhibition curves were shown for barramundi ( Lates calcarifer), coho salmon ( Oncorhynchus kisutch), Southern Bluefin tuna ( Thunnus maccoyii), tilapia ( Oreochromis mossambicus), and seabream ( Pagrus auratus) IGF-I. The assay was then used to measure stress related changes in different aquacultured fish species. Salt water acclimated Atlantic salmon smolts ( Salmo salar) bathed for 2 h in fresh water showed significantly lower IGF-I concentrations than control smolts two days after the bath (53.1 compared to 32.1 ng/ml), with levels of IGF-I also lower in smolts exhibiting stunted growth (stunts). Capture and confinement of wild tuna in sea-cages resulted in a significant decrease in IGF-I levels (28 ng/ml) when compared to tuna captured and sampled immediately (48 ng/ml), but had recovered to starting levels after 3 weeks (43 ng/ml). Handling and isolation in silver perch ( Bidyanus bidyanus) led to a gradual decline in IGF-I over a 12 h period (36–19 ng/ml) but showed signs of recovery by 24 h (24 ng/ml) and had recovered fully 72 h after treatment (40 ng/ml). A similar trial in black bream ( Acanthopagrus butcherii) showed comparable results with IGF-I levels gradually decreasing (40–26 ng/ml) over 24 h, results that were mirrored by cortisol concentrations which increased during this time (1–26 ng/ml). In the studies presented here changes in IGF-I levels were not observed for at least 3 h after exposure to the stressor. We suggest this is due to the endocrine nature of IGF-I regulation and the clearance rate of IGF-I in vivo.

Influence of acute and chronic exercise on insulin-like growth factor-I in healthy active elderly men and women.

We examined the influence of physical activity (PA) and acute resistance exercise on insulin-like growth factor I (IGF-I) in 39 healthy, independent, community-dwelling elderly volunteers (14 men and 25 women) aged from 66 to 84. In a longitudinal non-interventional study, we compared the fluctuations in IGF-I levels and changes in habitual PA over a 6-month period. PA was evaluated by a questionnaire QAPSE (Questionnaire d'Activité Physique Saint-Etienne), and expressed by two activity indices: mean habitual daily energy expenditure (MHDEE), and daily energy expenditure corresponding to leisure time sports activities (sports activity index). In an experimental design we compared IGF-I levels before, at 1 and 15 minutes after short quadriceps muscle exertion (10 consecutive repetitions) carried out with optimal muscle power development. Changes in IGF-I levels over a 6-month period were positively related to changes in MHDEE (r = 0.41; p<0.01), and sports activity (r = 0.40; p<0.02). When analyzed by gender, these correlations were still statistically significant in women (r = 0.39; p = 0.05 and r = 0.41; p<0.05), but not in men (r = 0.36; p = 0.21 and r = 0.20; p = 0.50). No changes (p = 0.17) were observed in serum IGF-I concentrations after the acute exercise protocol. These findings indicate that IGF-I levels are positively related to fluctuations in habitual PA, at least in women. Further research is needed to establish the best intensity and duration of exercise training to induce these changes.

Increased Expression of Insulin-like Growth Factor-I in Serum and Liver after Recombinant Human Growth Hormone Administration in Thermally Injured Rats

Background. Recombinant human growth hormone (rhGH) has been shown to modulate the hypermetabolic response and the hepatic acute-phase response after thermal injury. In vitro studies, however, demonstrated that rhGH activates insulin-like growth factor-I (IGF-I) gene transcription and production, suggesting that rhGH may exert some of its effects indirectly through IGF-I stimulation. The purpose of this study was to determine the effects of rhGH on serum and hepatic IGF-I in thermally injured rats.Methods. Sprague–Dawley rats (56 males) receiving a 60% TBSA third-degree scald burn were randomly divided to receive either rhGH (2.5 mg/kg/day im) or saline (control). Rats were sacrificed on postburn days 1, 2, 5, and 7 and serum IGF-I, hepatic IGF-I mRNA, and IGF-I protein concentration were measured. The physiologic response to changes in IGF-I levels was evaluated by measuring hepatocyte proliferation, total liver protein concentration, and muscle dry/wet weights.Results. Serum IGF-I was increased from postburn day 1 through day 7 in rats receiving rhGH compared to controls (P < 0.05). Hepatic IGF-I mRNA and IGF-I protein expression were increased from day 1 to 7 after burn in animals receiving rhGH when compared to controls (P < 0.05). Recombinant hGH increased hepatocyte proliferation at 5 days and total liver protein concentration at 5 and 7 days postburn compared to controls (P < 0.05). Muscle dry/wet weights increased in rats receiving rhGH at 7 days after burn compared to controls (P < 0.05).Summary. Liver and serum IGF-I levels decreased after a thermal injury. Recombinant hGH attenuated this decrease by stimulating hepatic IGF-I expression. Increases in IGF-I were associated with increases in hepatocyte proliferation and protein concentration in liver and muscle.Conclusion. We suggest that rhGH modulates the hypermetabolic response through IGF-I stimulation in the hepatic parenchyma.

Relationship between Plasma IGF-I Levels,in VitroCorrelates of Immunity, and Human Senescence

Insulin-like growth factor-I (IGF-I) is a polypeptide mitogen which is regulated by growth hormone (GH). IGF-I mediates many of the biological functions of GH, including the maintenance of lymphoid mass and functions. Since GH secretion declines with age, we asked whether changes in the availability of IGF-I might contribute to age-associated alterations in immune functions. As a first step, we examined relationships between plasma levels of IGF-I andin vitrocorrelates of immunity in young and elderly subjects. Heparinized plasma and lymphocytes were collected from the peripheral blood of 34 healthy young (aged 27 ± 0.9 years, mean ± SEM) and 41 elderly (79 ± 1.3 years) volunteers (31 males and 44 females in total). Plasma levels of IGF-I, measured by radioimmunoassay after the removal of IGF-I-binding proteins, were reduced among elders compared to young controls (138 ± 8.7 ng/mL vs 80.2 ± 4.7 ng/mL,P< 0.001). The number of circulating lymphocytes did not change with age. The proliferative response ([3H]thymidine uptake into DNA) of T-cells to concanavalin A and B-cells to pokeweed mitogen were reduced among elders (P< 0.05). An increased spontaneous antitumor natural killer (NK) activity (P< 0.001) was accompanied by a higher percentage of CD16+NK cells among lymphocytes in older subjects (P< 0.001). The NK cell number was positively related to IGF-I levels in young volunteers but not among elders. Correlation analysis demonstrated a highly significant relationship between plasma IGF-I levels and T-cell (but not B-cell) proliferative response during aging (r= 0.492,P< 0.001). Our results imply that reduced immunocompetence may be one of the consequences of reduced IGF-I levels in human aging. Among the three types of immune cells tested, the T-cells were most sensitive to fluctuations in IGF-I levels. Reduced IGF-I availability may be one of the determinants of the decline in T-cell-mediated immune function in the elderly. To our knowledge, this is the first report presenting correlative data on concurrent changes in IGF-I levels and immune parameters in human aging.