Higher Serum Insulin-like Growth factor-I Levels Research Articles

温度、盐度及其互作效应对吉富罗非鱼血清IGF-I与生长的影响

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

Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome

Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group. Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.

Serum levels of IGF-I and BRCA penetrance: a case control study in breast cancer families

High serum levels of insulin-like growth factor I (IGF-I) are associated with an increased risk of sporadic breast cancer (BC). The aim of the present work is to evaluate the association between IGF-I and hereditary BC risk, using a case-control approach. The work represents an "ad interim" cross-sectional analysis of an ongoing study with a prospective design whose aim is to recruit a cohort of women belonging to high genetic risk families to test potential modulators of penetrance and prognosis. The odd of exposure to high serum IGF-I levels among women with a previous diagnosis of BC ("cases") was compared with the odd among unaffected "controls". The odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, controlling for confounders. We analysed 308 women (209 cases and 99 controls) at high genetic risk of BC. The adjusted OR of BC for the upper tertile of serum IGF-I versus the lowest one was 3.5 (95%CI 1.4-8.8). Excluding from the analysis 64 women under current Tamoxifen or GnRH analogues treatment, the adjusted OR of BC became 3.7 (95%CI 1.4-9.9). The association became stronger restricting the analysis to the 161 women (97 cases and 64 controls) with a proven BRCA mutation. If confirmed by a prospective approach, the association between IGF-I and familial BC will open further options for reducing BC risk in susceptible women.

Advantages and disadvantages of GH/IGF-I combination treatment

Growth hormone (GH) is the primary regulator of insulin-like growth factor-I (IGF-I) production in a wide variety of tissues. There is much overlap in the endocrine, metabolic and anabolic effects of GH and IGF-I but both hormones have divergent effects on glucose metabolism, insulin sensitivity and differentiation of prechondrocytes. Theoretically combined administration of GH and IGF-I may be more effective than GH alone or IGF-I alone. Arguments in favor for this are: 1] Clearance of IGF-I may be markedly altered by the co-administration of GH and this will provide sustained actions of IGF-I. 2] Higher serum IGF-I levels are achieved with a combination treatment of GH and IGF-I than with GH treatment alone or IGF-I alone. In addition, combination therapy may have additive or synergistic effects. 3] The combination GH and IGF-I counteracts disadvantageous effects on glucose metabolism of either GH alone or IGF-I alone. 4] GH may exert direct actions on tissues independently from IGF-I. 5] Combination of GH and IGF-I may be more effective in improving tissue IGF-I levels. The combination therapy of GH and IGF-I might be beneficial in growth retardation, in certain specific subgroups of critically ill or catabolic patients and in the treatment of GH-deficient subjects with the metabolic syndrome and/or manifest diabetes. It is at present unknown whether an optimal balance between safety and efficacy can be achieved with the combination therapy of GH and IGF-I, since this combination has been evaluated in only a small number of patient populations and in studies of a relatively short duration. In addition, a disadvantage may be the financial costs of combination therapy of GH and IGF-I. In conclusion, there are many reasons for believing that administration of the combination therapy of GH and IGF-I could have advantages above GH alone or IGF-I alone. However, determination of whether co-administration of GH and IGF-I indeed is superior to either agent alone awaits further study.

Serum insulin-like growth factor I and ischemic brain injury

Serum insulin-like growth factor I (IGF-I), which is mostly produced by the liver, has recently been shown to have the unexpected ability to modulate normal brain function as well as brain response to injury. Moreover, serum IGF-I levels are modified in many brain diseases, including stroke. However, whether these modifications are related to the disease process remains uncertain. We now examined a potential relationship between serum IGF-I and ischemic brain injury after middle cerebral artery occlusion (MCAo) and reperfusion in mice with either high or low serum IGF-I levels prior to insult. Surprisingly, we found that chronic high serum IGF-I correlates with increased brain infarct size following MCAo, while low levels correlate with reduced lesion size. Immunocytochemistry and immunoblot analyses revealed that levels of phosphorylated (i.e., activated) MAPK, known to be associated with the severity of ischemic brain injury, were increased in IGF-I treated mice. No overall effect of IGF-I treatment on IGF family mRNA expression in the brain was observed. Altogether, these results indicate that serum IGF-I levels negatively correlate with stroke outcome. Therefore, lowering serum IGF-I levels in aging mammals, including humans, may be beneficial against the increased risk of stroke associated to old age.

High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age

Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses. Thirty-six prepubertal short SGA children were the subjects of this study. Subjects received 1 (group A) or 2 (group B) mg GH/m(2).d. At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured. After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P < 0.009). In group B, maximum GH levels increased from 43.9-161 mU/liter (P < 0.0002), and in group A, from 57.2-104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A. Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.

Serum Insulin-Like Growth Factor-I Levels and Prostatic Intraepithelial Neoplasia: A Clue to the Relationship Between IGF-I Physiology and Prostate Cancer Risk

Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are associated with precancerous lesions of the prostate. We conducted a case-control study to determine whether high serum IGF-I levels were associated with the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) among patients who presented for prostate biopsy because of an abnormal serum prostate-specific antigen level or digital rectal exam. We measured serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) prior to prostate biopsy and compared them between 103 men with HGPIN (cases) and 205 men with normal prostate histology (controls). The mean IGF-I level in patients with HGPIN (130.2 ng/mL) was significantly higher compared with controls (118.8 ng/mL, P = 0.01). The mean IGFBP-3 level in patients with HGPIN (2,393.9 ng/mL) was also higher compared with controls (2,276.0 ng/mL, P = 0.06). After adjusting for age, prostate-specific antigen, digital rectal examination, and ethnic background, the odds ratio for a HGPIN diagnosis among men in the highest relative to the lowest quartile of serum IGF-I level was 1.94 (95% confidence interval, 1.0-3.7; P = 0.04). The potential association between a high serum IGF-I level and the presence of HGPIN may represent an important clue to understanding the basis for the relationship between IGF-I physiology and prostate cancer risk. Larger studies will be required to confirm this relationship.

Insulin-like growth factor I, insulin-like growth factor binding protein 3, and urologic measures of benign prostatic hyperplasia.

Laboratory studies suggest that insulin-like growth factor I (IGF-I) promotes prostatic growth. The authors evaluated the association between benign prostatic hyperplasia and IGF-I and its binding protein IGFBP-3 in community-dwelling men to determine whether this laboratory finding is manifest at the population level. Participants (n = 471) were Olmsted County, Minnesota, Caucasian males aged 40-79 years in 1990. Urologic measures were assessed from the International Prostate Symptom Score, peak urinary flow rates, prostate volume, and serum prostate-specific antigen (PSA), and serum IGF-I and IGFBP-3 levels were measured. After adjustment for age, the relative odds (odds ratios) of an abnormal urologic measure in men with high versus low serum IGF-I levels were 0.98 (95% confidence interval (CI): 0.66, 1.45) for a symptom score of >7, 1.14 (95% CI: 0.72, 1.80) for a peak urinary flow rate of <12 ml/second, 1.11 (95% CI: 0.72, 1.72) for a prostate volume of >30 ml, and 0.71 (95% CI: 0.46, 1.09) for a PSA level of >1.4 ng/ml. A low IGFBP-3 level was associated with an enlarged prostate (odds ratio = 1.72, 95% CI: 1.05, 2.82), after simultaneous adjustment for IGF-I and age, but not with other urologic measures. These data do not provide evidence for an association between benign prostatic hyperplasia and serum IGF-I.

Significance of serum vascular endothelial growth factor, insulin-like growth factor-I levels and nitric oxide activity in breast cancer patients

Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF and IGF-I levels were higher in patients with metastatic disease than in those with nonmetastatic disease or in controls ( P<0.001). Serum nitrate+nitrite levels were higher in patients with metastatic and nonmetastatic disease than in controls ( P<0.001). Patients with visceral metastasis and local metastasis had higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis ( P<0.05). In the metastatic disease group, there was a positive correlation between serum VEGF levels and nitrate+nitrite levels ( r=0.436, P<0.05). Within the group with nonmetastatic disease, premenopausal patients had higher serum IGF-I levels than did postmenopausal patients ( P<0.001). NO may involve an angiogenic process that is stimulated by VEGF in breast carcinoma. Larger studies are required to clarify these suggestions.

Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance).

Serum gonadotrophins. androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 microg/kg per day to the boys and 120 microg/kg per day to the adult patient. In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 microg/kg per day. Stopping the IGF-I administration in this patient, according to the protocol, led to a return to pretreatment serum levels and testicular and penile size. This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.

Functional Antagonism between Endogenous Mouse Growth Hormone (GH) and a GH Analog Results in Dwarf Transgenic Mice*

A dwarf transgenic mouse (DTM) line has been established in which mice express relatively high levels of a mutated bovine (b) GH gene. This bGH analog binds to mouse liver membrane preparations with an affinity similar to that of wild-type bGH. The mean growth ratio of these mice is approximately 0.7 relative to that of their nontransgenic littermates. Serum insulin-like growth factor-I (IGF-I) levels of DTM were found to be approximately half those in nontransgenic littermates. Liver GH receptor levels were up-regulated in DTM or wild-type bGH transgenic mice. Pituitary GH levels were negatively correlated with serum IGF-I concentrations. Wild-type bGH transgenic mice contain relatively high serum IGF-I and low pituitary GH levels, whereas DTM possess low serum IGF-I and high pituitary GH levels. The decrease in serum IGF-I resulting from the interaction between the bGH analog, the endogenous mouse GH, and GH receptor(s) apparently leads to a dwarf phenotype. These data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH.