OBJECTIVE: The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging. METHODS: First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism. RESULTS: In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1. CONCLUSION Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.
Humans ; Animals ; Mice ; Insulin-Like Growth Factor I/pharmacology* ; Cellular Senescence ; Aging ; Hippocampus ; DNA Polymerase III

OBJECTIVETo identify the changes in serum insulin like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF-I and IGFBPs.

METHODSWe measured serum IGF-I and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n = 12), a remission stage group (RE, n = 12), an active stage group with glucocorticoid treatment (GNS, n = 12), and a normal control group (NC, n = 10).

RESULTS1) Compared to NC, serum levels of IGF-I and IGFBP-3 were decreased (P < 0.01); serum levels of IGFBP-1 and IGFBP-2 were increased (P < 0.01) in the ANS group. 2) Serum levels of IGF-I and IGFBP-3 were higher and IGFBP-1 and IGFBP-2 were lower in the RE Group than in theANS Group (P < 0.01). 3) Compared to the ANS group, serum levels of IGF-I and IGFBP-3 were increased (P < 0.01) and serum levels of IGFBP-1 and IGFBP-2 were decreased (P < 0.01) in the GNS group. 4) A correlation was found between serum levels of IGFBP-3 and albumin in the active stage group (r = 0.76, P < 0.01). There was also a correlation between serum levels of IGF-I and IGFBP-3 and an inverse correlation between the serum level of IGF-I and serum levels of IGFBP-1 and IGFBP-2 in the ANS group. No other correlations were observed.

CONCLUSIONSThe serum levels of IGF-I and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage. GC treatment may influence serum IGF-I and IGFBPs in children with NS. Changes in IGF-I and IGFBPs levels may play a role in the growth retardation of NS children.

Child ; Dexamethasone ; pharmacology ; Female ; Glucocorticoids ; pharmacology ; Humans ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Nephrotic Syndrome ; blood

OBJECTIVEIntrauterine growth retardation (IUGR) may contribute to the disorder of development of fetal brains. L-arginine has been known to be effective in blood vessel distension and improving the blood circulation of placentas. Recent studies have shown that L-arginine can ameliorate the placental hypoxia and improve the development of fetus. This study aimed to explore the effects of L-arginine on the expression of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-3(IGFBP3)and IGF-I mRNA in brains of IUGR rats and the possible mechanisms of L-arginine.

METHODSThirty-six pregnant rats were randomly assigned into four groups: Control, Model, Low dose L-arginine (100 mg/kg) and High-dose L-arginine (200 mg/kg L-arginine) groups (n=9 each). IUGR was induced by passive smoking in rats from the last three groups. L-arginine was administered for the last two groups between days 8 and 20 of gestation. On day 21 of gestation, the pup rats were delivered by cesarean section. The levels of IGF-I, IGF-II and IGFBP3 in the brains of pup rats were measured by enzyme-linked immunoadsordent assay (ELISA) and the expression of IGF-I mRNA was detected by fluorescence quantitative PCR (FQ-PCR).

RESULTSThe levels of IGF-I, IGF-II and IGF-I mRNA expression in the Model group were significantly lower than in the Control group, with the IGF-I levels of 0.789 +/- 0.062 ng/mg vs 0.947 +/- 0.042 ng/mg, the IGF-II levels of 0.270 +/- 0.020 ng/mg vs 0.374 +/- 0.015 ng/mg and the IGF-I mRNA expression of (13.12 +/- 1.39) x 10(4) cps/mug RNA vs (21.28 +/- 3.54) x 10(4) cps/mug RNA (P < 0.01). In contrast, the IGFBP3 levels in the Model group were significantly higher than in the Control group (0.253 +/- 0.011 ng/mg vs 0.089 +/- 0.015 ng/mg; P < 0.01). Low or high dose L-arginine treatment increased significantly the IGF-I levels from 0.789 +/- 0.062 ng/mg (Model group) to 0.937 +/- 0.067 ng/mg (low dose group) or 0.858 +/- 0.077 ng/mg (high dose group), the IGF-II levels from 0.270 +/- 0.020 ng/mg (Model group) to 0.318 +/- 0.018 ng/mg (low dose group) or 0.354 +/- 0.021 ng/mg (high dose group) and the IGF-I mRNA expression from (13.12 +/- 1.39) x 10(4) cps/mug RNA (Model group) to (19.24 +/- 2.48) x 10(4) cps/mug RNA (low dose group) or (17.35 +/- 2.30) x 10(4) cps/mug RNA (high dose group) (P < 0.01). The IGFBP3 levels were significantly reduced after low or high dose L-arginine treatment (0.132 +/- 0.006 ng/mg or 0.146 +/- 0.009 ng/mg) compared with those of the Model group (0.253 +/- 0.011 ng/mg) ( P < 0.01).

CONCLUSIONSL-arginine can increase the levels of IGF-I and IGF-II and the IGF-I mRNA expression, and decrease the IGFBP3 level in the brain of rats with IUGR induced by passive smoking, thereby offering protective effects against IUGR.

Animals ; Arginine ; pharmacology ; therapeutic use ; Female ; Fetal Growth Retardation ; metabolism ; prevention & control ; Insulin-Like Growth Factor Binding Protein 3 ; analysis ; Insulin-Like Growth Factor I ; analysis ; genetics ; Insulin-Like Growth Factor II ; analysis ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

OBJECTIVES: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. METHODS: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. RESULTS: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (<i>Pi>>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (<i>Pi><0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (<i>Pi><0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (<i>Pi><0.05), the FGF23 level was positively correlated with the IGF-1 level (<i>Pi><0.05), and the Klotho level was positively correlated with the FGF23 level (<i>Pi><0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (<i>Pi>>0.05). CONCLUSIONS The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
Child ; Humans ; Human Growth Hormone/pharmacology* ; Insulin-Like Growth Factor I/pharmacology* ; Fibroblast Growth Factor-23 ; Prospective Studies ; Growth Disorders ; Phosphates/pharmacology* ; Body Height

Animals ; Benzodiazepines ; pharmacology ; Ducks ; physiology ; Growth Hormone ; blood ; Insulin-Like Growth Factor I ; metabolism ; Serum ; metabolism ; Weight Gain ; drug effects

Body Height ; Child ; Female ; Ghrelin ; pharmacology ; Growth Disorders ; physiopathology ; Growth Hormone-Releasing Hormone ; pharmacology ; Human Growth Hormone ; blood ; physiology ; urine ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; physiology ; Male

OBJECTIVESTo study the influence of insulin on IGF-I and IGFBP-I secretion of the human endometrial stromal cells.

METHODSLate proliferative phase endometrial stromal cells were isolated from endometrium tissues and then cultured for 24 h in Hams F-12 only as a control and in Hams F-12 with different concentrations of estradiol (E2) and insulin (INS) as treated groups. Simultaneously, the endometrial stromal cells from late secretory phase endometrium were cultured for 24 h in Hams F-12 only as a control and in Hams F-12 supplemented with different concentrations of progesterone (P) and insulin as treated groups. After 24 h of culturing, the mediums were collected for either IGF-I or IGFBP-I assays.

RESULTThe concentrations of IGF-I in medium from cultured endometrial stromal cells in the proliferative phase were 0.78 +/- 0.47 ng/ml in the hormone-free control group; 1.44 +/- 0.59 ng/ml and 1.39 +/- 0.33 ng/ml in 100 pg/ml E2 group and 20 microU/ml INS group, which was higher than that of the control group (P < 0.05 and P < 0.01, respectively). The IGF-I concentration in the 100 microU/ml INS group was 2.03 +/- 0.53 ng/ml, which was higher than that of the 20 micro U/ml INS group (P < 0.01). Levels of IGF-I in the 100 pg/ml E2 plus 20 microU/ml INS group was 2.18 +/- 0.36 ng/ml, which was significantly higher than that of the 20 microU/ml INS and 100 pg/ml E2 group (P < 0.01), but lower than that of the 100 pg/ml E2 plus 100 microU/ml INS group (3.42 +/- 0.75 ng/ml), P < 0.01. The concentration of IGFBP-I in medium from cultured endometrial stromal cells in the secretory phase was 2.50 +/- 1.39 ng/ml in the hormone-free control group and 5.44 +/- 2.09 ng/ml in the 10 pg/ml P group, which was significantly higher than that of the control (P < 0.01). IGFBP-I concentration in 20 microU/ml INS group was 0.16 +/- 0.58 ng/ml, which was lower compared with control, but higher compared with the 100 microU/ml INS group (P < 0.01). The level of IGFBP-I in the 10 ng/ml P plus 20 microU/ml INS group was 2.10 +/- 1.17 ng/ml, lower compared with the 10 ng/ml P group, but higher compared with the 10 pg/ml P plus 100 microU/ml INS group, P < 0.01.

CONCLUSIONSInsulin can stimulate basal (without hormone) and E2-stimulated IGF-I secretion in cultured stromal cells from human late proliferative endometrium in a dose-dependent manner. Insulin can suppress basal (without hormone) and P-stimulated IGFBP-I secretions in cultured stromal cells from human secretory endometrium in a dose-dependent manner.

Cells, Cultured ; Dose-Response Relationship, Drug ; Endometrium ; cytology ; drug effects ; secretion ; Estradiol ; pharmacology ; Female ; Humans ; Insulin ; pharmacology ; Insulin-Like Growth Factor Binding Protein 1 ; secretion ; Insulin-Like Growth Factor I ; secretion ; Progesterone ; pharmacology ; Stromal Cells ; drug effects ; secretion

To explore the relationship between Insulin-like growth factor (IGF)-I , -II and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley (SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF- I, -II (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF- I in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-I during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-I was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-II took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-II in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-I, -II mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-I , -II and lung development in newborns. The IGF-II works at early stage and the that of IGF- I works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.
Animals ; Animals, Newborn ; Dexamethasone ; pharmacology ; Female ; Insulin-Like Growth Factor I ; biosynthesis ; genetics ; Insulin-Like Growth Factor II ; biosynthesis ; genetics ; Lung ; embryology ; growth & development ; metabolism ; Male ; Pregnancy ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tretinoin ; pharmacology

OBJECTIVETo explore the effects of amino acid solution and recombinant human growth hormone on growth hormone/insulin like growth factor-1 (GH/IGF-1) axis after partial hepatectomy in rats with liver cirrhosis.

METHODSSix normal rats severed as normal group, while 30 rats with liver cirrhosis were randomly divided into preoperation group, 1 day postoperative group, 8.5% Novamin PN for 5 days postoperative group, 10% Hepa PN for 5 days postoperative group and rhGH + 10% Hepa PN for 5 days postoperative group. Liver function, blood glucose and serum GH, IGF-1, IGFBP-3 were determined. ALB mRNA, IGF-1 mRNA and IGFBP-3 mRNA levels in liver tissues were detected by RT-PCR. Liver Ki67 immunohistochemistry staining was studied.

RESULTSCompared with the 8.5% Novamine PN group, serum ALT [(103 +/- 23) IU/L vs (154 +/- 45) IU/L], ALP [(571 +/- 92) IU/L vs (972 +/- 252) IU/L], GH [(1.55 +/- 0.12) ng/ml vs (1.81 +/- 0.11) ng/ml] level were lower (P < 0.05), serum IGF-1 [(966 +/- 55) ng/ml vs (813 +/- 43) ng/ml] and IGFBP-3 [(8.1 +/- 0.3) ng/ml vs (6.9 +/- 0.2) ng/ml] level and the expression of hepatic ALB mRNA (1.24 +/- 0.06 vs 1.02 +/- 0.09), IGF-1 mRNA (0.85 +/- 0.00 vs 0.60 +/- 0.03), IGFBP-3 mRNA (0.69 +/- 0.02 vs 0.58 +/- 0.09) were higher in the 10% Hepa PN group (P < 0.05), but there was no difference in liver Ki67 labeling index [(4.8 +/- 0.3)% vs (4.4 +/- 0.4%)] (P > 0.05). Compared with the 10% Hepa PN group, serum ALP [(434 +/- 41) IU/L vs (571 +/- 92) IU/L] was much lower (P < 0.05), serum ALB [(37.0 +/- 1.8) g/L vs (32.8 +/- 1.2) g/L], blood glucose [(7.6 +/- 1.3) mmol/L vs (4.9 +/- 0.7) mmol/L], GH [(3.00 +/- 0.61) ng/ml vs (1.55 +/- 0.12) ng/ml], IGF-1 [(1100 +/- 32) ng/ml vs (966 +/- 55) ng/ml], IGFBP-3 [(9.3 +/- 0.2) ng/ml vs (8.1 +/- 0.3) ng/ml] level, the expression of hepatic ALB mRNA (1.35 +/- 0.04 vs 1.24 +/- 0.06), IGF-1 mRNA (0.97 +/- 0.00 vs 0.85 +/- 0.00) and liver Ki67 labeling index [(5.4 +/- 0.3)% vs (4.8 +/- 0.3%)] were higher (P < 0.05) in the rhGH + 10% Hepa PN group.

CONCLUSIONSAmino acid solution and recombinant human growth hormone can influence the GH/IGF-1 axis in rats with liver cirrhosis. It may be helpful in selecting and evaluating nutrient by measuring the serum IGF-1 and IGFBP-3 level.

Amino Acids ; pharmacology ; therapeutic use ; Animals ; Human Growth Hormone ; pharmacology ; therapeutic use ; Insulin-Like Growth Factor Binding Protein 1 ; blood ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Liver Cirrhosis, Experimental ; blood ; therapy ; Male ; Parenteral Nutrition, Total ; methods ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; therapeutic use

The objective was to explore the feasibility of differentiation of human umbilical cord blood mononuclear cells into endothelial cells induced by cytokines in vitro and to study the possibility of using cord blood stem cells in ischemic diseases therapy. The cells were isolated from umbilical cord blood by using lymphocyte separation solution, and committedly differentiated by using VEGF, bFGF and IGF-I in a liquid culture system. The results showed that the combination of cytokines produced a large number of caudated adherent cells and flow cytometric analysis revealed endothelial marker vWF expressed in about 80% cells, and the endothelial -specific Weibel-Palade body was detected in the cytoplasm by electronic microscope. It is concluded that human umbilical cord blood mononuclear cells may be induced to differentiate into endothelial cells induced by VEGF, bFGF and IGF-I. Human umbilical cord blood MNC may be an ideal source of adult stem cells for the treatment of the ischemic disease.
Cell Differentiation ; drug effects ; Cells, Cultured ; Endothelial Cells ; cytology ; ultrastructure ; Fetal Blood ; cytology ; Fibroblast Growth Factor 2 ; pharmacology ; Flow Cytometry ; Humans ; Insulin-Like Growth Factor I ; pharmacology ; Leukocytes, Mononuclear ; cytology ; Microscopy, Electron ; Vascular Endothelial Growth Factor A ; pharmacology