PURPOSE: The aim of this study was to investigate the clinical significance of 7 circulating adipokines according to body mass index (BMI) in Korean men with localized prostate cancer (PCa) undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Sixty-two of 65 prospectively enrolled patients with clinically localized PCa who underwent RP between 2015 and 2016 were evaluated. Patients were classified into 2 groups according to their BMI: non-obese (< 25 kg/m²) and obese (≥25 kg/m²). The adipokines evaluated were interleukin-2, insulin-like growth factor 1 (IGF-1), chemerin, C-X-C motif chemokine 10, adiponectin, leptin, and resistin. Multivariate logistic regression analysis was used to identify the independent predictors of advanced tumor stage. RESULTS: We found that obese patients with PCa who underwent RP had a higher incidence of tumors with a high Gleason score (≥8), pathological T3 (pT3) stage, and positive extraprostatic extension than patients with a normal BMI. Additionally, patients with obesity showed significantly lower serum adiponectin and higher serum leptin levels, but did not show differences in other adipokines. Multivariate analysis demonstrated that IGF-1 (odds ratio [OR]=1.03) was identified as a predictor of advanced tumor stage (≥pT3) in the overall population. However, only leptin remained an independent predictive factor for advanced tumor stage (≥pT3) (OR=1.15) in patients with obesity. CONCLUSIONS: In conclusion, our results indicate that a higher leptin level in obese men can be considered a risk factor for aggressive PCa. This prospective study provides greater insight into the role of circulating adipokines in Korean patients with PCa undergoing RP, particularly in patients with obesity.
Adipokines ; Adiponectin ; Body Mass Index ; Humans ; Incidence ; Insulin-Like Growth Factor I ; Interleukin-2 ; Leptin ; Logistic Models ; Male ; Multivariate Analysis ; Neoplasm Grading ; Obesity ; Passive Cutaneous Anaphylaxis ; Prospective Studies ; Prostate ; Prostatectomy ; Prostatic Neoplasms ; Resistin ; Risk Factors

OBJECTIVETo study the effects of maternal folate deficiency on fetal growth and development and the methylation profiles of insulin-like growth factor system in the offspring rats.

METHODSTwenty-two Sprague-Dawley female rats were randomly assigned to two groups: a folate deficient group (n=12) and a control group (n=10). They were fed with folate deficient and normal diet respectively. Dams were mated after 2 weeks of feeding. Eight female rats from each group were pregnant. On the 20th day of gestation, the fetuses were delivered by caesarean section. Thirty-two fetal rats from each group were randomly selected and the body length and weight were measured. Eight fetal rats from each group were randomly selected and ELISA was used to measure the level of folate content, IGF-1 and IGFBP-3 in the fetal brain and liver. Three fetal rats from each group were randomly selected and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) was used to detect the methylation level of insulin-like growth factor system in the fetal brain and liver. ELISA was used to measure the level of IGF-1 and IGFBP-3 in the maternal serum from both groups.

RESULTSThe mean fetal length and weight were lower in the folate deficient group than in the control group (P<0.05). The levels of IGF-1 and IGFBP-3 in the maternal serum, as well as folate content and IGFBP-3 in the fetal brain and liver were significantly lower in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-2, IGFBP-5, IGFBP-6 and IGFBP-7 in the fetal brain were higher in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-3 and IGFBP-5 in the fetal liver were higher in the folate deficient group than in the control group. The methylation of IGF-2 gene showed a significant reduction in the folate deficient group (P<0.05).

CONCLUSIONSMaternal folate deficiency may cause retardation of growth and development of the offspring, which is possibly associated with the changes of methylation profiles of insulin-like growth factors.

Animals ; Brain ; metabolism ; DNA Methylation ; Female ; Fetal Development ; Fetus ; metabolism ; Folic Acid Deficiency ; metabolism ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Liver ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA).

METHODSA total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups.

RESULTSΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function.

CONCLUSIONSrhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.

Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Infant, Small for Gestational Age ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use

OBJECTIVETo study the correlation between serum insulin-like growth factor-1 (IGF-1) level and feeding difficulties in preterm infants.

METHODSA retrospective analysis was performed on 200 preterm infants born between January 2013 and January 2014. Venous blood samples were obtained within 24 hours after birth to determine the serum level of IGF-1. The correlation between IGF-1 level and feeding difficulties in preterm infants was analyzed by single-factor analysis and multivariate logistic regression analysis.

RESULTSThe serum IGF-1 level in the feeding difficulty group was significantly lower than that in the control group (28±4 ng/mL vs 63±8 ng/mL; P<0.05). Results of multivariate logistic regression analysis showed that high gestational age and birth weight were protective factors for feeding difficulties in preterm infants, whereas asphyxia, delayed initiation of feeding, use of aminophylline, perinatal infection and decreased IGF-1 level were risk factors.

CONCLUSIONSThe level of serum IGF-1 is correlated with feeding difficulties in premature infants. A reduced IGF-1 level increases the risk of feeding difficulties.

Birth Weight ; Breast Feeding ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; blood ; Insulin-Like Growth Factor I ; analysis ; Logistic Models ; Male ; Retrospective Studies

OBJECTIVETo explore the correlation between methylation of insulin-like growth factor 1 (IGF-1) gene promoter and its placenta-specific expression and fetal macrosoma.

METHODSOne hundred twenty nine healthy pregnant women were recruited between April 2011 and March 2012. Baseline data were collected with self-report questionnaires. Real-time quantitative PCR was used to determine the expression of IGF-1 mRNA in the placenta. Methylation level of the IGF 1 gene was determined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

RESULTSThe expression of IGF-1 in placenta and its methylation level showed no significant difference between macrosomic fetuses and controls. No linear correlation was found between IGF-1 mRNA expression and methylation level of IGF-1 promoter (r=0.128, P=0.295). IGF-1 promoter region in placenta showed a hypomethylation status. However, a positive correlation was found between IGF-1 expression and birth weight below 4260 g (r=0.264, P=0.022). The expression of IGF-1 mRNA was significantly higher in those with a birth weight below 4260 g, which suggested that placental IGF-1 expression may contribute to increased birth weight. In regard to fetal overgrowth, however, there seemed to be a negative correlation in which placental IGF-1 expression was downregulated to limit fetal overgrowth.

CONCLUSIONNo linear correlation was found between placental IGF-1 expression and methylation level of IGF-1 promoter with a hypomethylation status. The contribution of placental IGF-1 expression to birth weight is bidirectional. Increased expression seems to promote fetal growth, while decreased expressions may curb overgrowth, therefore control fetal growth in a relatively normal range.

Birth Weight ; DNA Methylation ; Female ; Fetal Macrosomia ; genetics ; Humans ; Infant, Newborn ; Insulin-Like Growth Factor I ; genetics ; Placenta ; metabolism ; Pregnancy ; Promoter Regions, Genetic ; RNA, Messenger ; analysis

OBJECTIVETo study the effect of L-alanyl-L-glutamine (Ala-Gln) on the levels of insulin-like growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) in the intestinal tissues of low-birth-weight (LBW) newborn rats with hypoxia/reoxygenation-induced intestinal injury.

METHODSPregnant rats were fed with or without smoking. The rats born by those fed without smoking were included in group A; for the rats born by those fed with smoking, normal-birth-weight rats were included in group B, and LBW rats were randomly divided into control group (group C), hypoxia/reoxygenation (H/R) group (group D), and Ala-Gln group (group E). Each group consisted of 24 newborn rats. The rats in groups D and E received H/R treatment twice a day for three consecutive days to establish an intestinal injury model; the rats in group E were intraperitoneally injected with Ala-Gln (10 ml/kg) before daily H/R treatment, while those in groups C and D were given an equal dose of normal saline by intraperitoneal injections. On days 4, 7, and 10 after birth, 8 rats were sacrificed in each group to collect intestinal tissues. The IGF-1 levels in intestinal tissues were measured using ELISA, and IGF-1R levels were measured by immunohistochemistry.

RESULTSThere were no significant differences in IGF-1 and IGF-1R levels between groups A and B at all time points. The levels of IGF-1 and IGF-1R in group C kept increasing, were higher than those in other groups on day 7 (P<0.05), and reached a normal level on day 10, without significant differences compared with those in groups A and B. Group D had significantly lower IGF-1 and IGF-1R levels than group C at all time points (P<0.05). The levels of IGF-1 and IGF-1R in group E were lower than those in group C on days 4 and 7 (P<0.05), but they increased to approximately the levels in group C and were significantly higher than those in group D on day 10.

CONCLUSIONSIntrauterine and postnatal hypoxia may induce intestinal injury in LBW newborn rats, and parenteral administration of high-dose Ala-Gln can reduce hypoxia-induced intestinal injury. Therefore, Ala-Gln has a protective effect against hypoxia-induced intestinal injury.

Animals ; Birth Weight ; Dipeptides ; pharmacology ; Female ; Hypoxia ; metabolism ; Insulin-Like Growth Factor I ; analysis ; Intestines ; chemistry ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Receptor, IGF Type 1 ; analysis

OBJECTIVETo explore the mechanism and effect of maternal high-fat diet before and during pregnancy on bone growth of neonatal offspring rats.

METHODSForty female Sprague-Dawley rats were divided into high-fat diet and control groups (n=20) that were fed with 35% high-fat diet and standard chow, respectively. After 8 weeks, 8 female rats from each group were sacrificed for liver pathological examinations and the other female rats were mated with male rats and fed continuously with 35% high-fat diet and standard chow throughout gestation, respectively. The body lengths (from apex nasi to end of tail) of the offspring rats from both groups were measured within 24 hours after birth. Enzyme-linked immunosorbent assay was used to detect serum insulin-like growth factor (IFG-I) levels. Liver pathological changes were observed under a light microscope. The expression of insulin receptor substrate 1 (IRS-1) and phosphorylation IRS-1 (Phospho-IRS-1) in tibia and femur samples were detected by immunohistochemistry. The expression of mitogen-activated protein kinase (MAPK) and phosphorylation MAPK (Phospho-MAPK), phosphatidylinositol 3-kinase (PI3K) and phosphorylation PI3K (Phospho-PI3K), protein kinase B (AKT1) and phosphorylation AKT1 (Phospho-AKT1) in tibia and femur samples were detected by Western blot.

RESULTSThe offspring rats from the high-fat diet group showed a significant shorter body length compared with those from the control group (P<0.05). The level of serum IGF-I in offspring rats from the high-fat diet group decreased by 20.1% in comparison to those from the control group, but there was no significant difference between the two groups (P>0.05). Fatty degeneration was found in livers of both high-fat diet-fed maternal rats and their offspring rats under a light microscope. There were no significant differences in IRS-1 and Phospho-IRS-1 expression in chondrocytes of tibia and femur samples between the offspring rats of the two groups (P>0.05). The protein expression of MAPK in chondrocytes of tibia and femur samples of offspring rats from the high-fat diet group was higher than that from the control group (P<0.05). There were no significant differences of PI3K and AKT1/Phospho-AKT1 between the offspring rats of the two groups (P>0.05).

CONCLUSIONSA maternal high-fat diet before and during pregnancy may affect the bone growth of offspring rats in utero, which is possibly associated with the decreased IGF-I level. However, further study on the exact mechanism of IGF-I on the bone growth is needed.

Animals ; Bone Development ; Diet, High-Fat ; Female ; Insulin-Like Growth Factor I ; analysis ; Liver ; pathology ; MAP Kinase Signaling System ; Maternal Nutritional Physiological Phenomena ; Phosphatidylinositol 3-Kinases ; physiology ; Pregnancy ; Proto-Oncogene Proteins c-akt ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the changes in anxiety-like behavior among rats in the recovery stage after hypoxic-ischemic brain damage (HIBD) during the perinatal period and to investigate the effect of insulin-like growth factor 1 (IGF-1) on the long-term anxiety-like behavior and its action mechanism among rats with HIBD.

METHODSNinety neonatal rats (7 days old) were randomly and equally divided into normal control, HIBD, and HIBD+IGF-1 groups. A neonatal rat model of HIBD was established by Rice method in the HIBD and HIBD+IGF-1 groups. The rats in the HIBD+IGF-1 group were intraperitoneally injected with IGF-1 (0.2 mg/kg) immediately after HIBD, and the other two groups were intraperitoneally injected with an equal volume of normal saline. The anxiety-like behavior was evaluated by elevated plus-maze test on postnatal days 21 and 28. The expression of tyrosine hydroxylase (TH) in the substantia nigra was measured by immunohistochemistry on postnatal days 14, 21, and 28.

RESULTSOn postnatal days 21 and 28, the open-arm time (OAT) and percentage of OAT for the HIBD and HIBD+IGF-1 groups were significantly lower than those for the normal control group (P<0.05), but there were no significant differences between the HIBD and HIBD+IGF-1 groups (P>0.05); the percentage of open arm entry showed no significant difference between the three groups (P>0.05). On postnatal day 14, there were no significant differences in percentage of TH immunostaining-positive area between the three groups (P>0.05). On postnatal days 21 and 28, the HIBD and HIBD+IGF-1 groups had significantly lower percentages of TH immunostaining-positive area than the normal control group (P<0.05), but there was no significant difference between the HIBD and HIBD+IGF-1 groups (P>0.05).

CONCLUSIONSHIBD in the perinatal period may cause the changes in anxiety-like behavior in adolescent rats, which may be related to decreased expression of TH in the substantia nigra. Neonatally given IGF-1 cannot improve the long-term anxiety-like behavior in rats after HIBD, and it does not affect TH expression in the substantia nigra. IGF-1 may not regulate the changes in long-term anxiety-like behavior in adolescent rats.

Animals ; Animals, Newborn ; Anxiety ; drug therapy ; Female ; Hypoxia-Ischemia, Brain ; psychology ; Immunohistochemistry ; Insulin-Like Growth Factor I ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Tyrosine 3-Monooxygenase ; analysis

Adolescent ; Body Height ; drug effects ; Child ; Female ; Growth Disorders ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
Animals ; Cattle ; Estradiol/blood ; Female ; Growth Hormone/blood ; Insulin/blood ; Insulin-Like Growth Factor Binding Protein 2/analysis ; Insulin-Like Growth Factor Binding Protein 3/analysis ; Insulin-Like Growth Factor Binding Protein 4/analysis ; Insulin-Like Growth Factor I/*analysis/physiology ; Liver/chemistry ; Pregnancy/metabolism/physiology ; Pregnancy, Animal/*metabolism/physiology ; Progesterone/blood ; Suppressor of Cytokine Signaling Proteins/analysis ; Thyroid Hormones/blood