PURPOSE: Insulin-like growth factor I(IGF-I) is a polypeptide mitogen and mediates growth effect of growth hormone(GH). The lack of daily variation of IGF-2 allows their measurements to be reliable in screening for growth disorders. The aims of this study are to evaluate the mean levels of IGF-I and also to evaluate whether IGF-I has diagnostic significance as a screening test in short stature children. METHODS: We studied 71 short stature children(Male 43, Female 28)whose test results were normal after GH provocation test(L-dopa and/clonidine). Control group was 13 children with GH deficiency(complete GH deficiency 6 cases, partial GH deficiency 7 cases). Serum GH level was measured with radioimmunoassay(RIA, Diagnostic system laboratories, USA) kit. and serum IGF-I level was measured with RIA kit(Nichols co., USA). RESULTS : 1) Study group included 71 short stature children(male 43, female 28) without GH deficiency and 13 short stature children with GH deficiency(complete GH deficiency 6, partial GH deficiency 7). 2) The height of 43 male children was below 50 percentile except in 3 cases. And 28 female children was below 50 percentile except 1 case. In Tanner standard growth curve. But, 7 male chidren with GH deficiency was below -1SD and 6 female children with GH deficiency was below -2SD. 3) Serum IGF-I level in short stature children without GH deficiency was seen to increase with age and serum IGF-1 level of female was higher than that of male. 4) Serum IGF-I level was correlated with height percentile in study group(male: Y=0.017X+0.243, r=0.294, P=0.03, female: Y=1.248X+0.716, r=0.384, P=0.01). 5) Serum IGF-I level was -2SD in most GH deficient children. Conclusions: The height was mostly below 50 percentile of the Tanner growth curve in short stature children without GH deficiency. Serum IGF-I level was weakly correlated with the height percentile in both male and female study group. But, serum IGF-I level has limited value of screening test in diagnosis of short stature. However, if serum IGF-I level below -2SD, it could be anti pate the sign for further evaluation of GH deficiency.
Child* ; Diagnosis ; Female ; Growth Disorders ; Humans ; Insulin-Like Growth Factor I* ; Insulin-Like Growth Factor II ; Male ; Mass Screening

PURPOSE: The insulin like growth factors (IGFs) circulate complexed to IGF-binding proteins(IGFBPs). IGFBP-3 is the major circulating IGFBP and is found primarily as a 150 kDa complex which contains an acid labile subunit(ALS), IGFBP-3, and IGF-I or IGF-II and is considered to be growth hormone(GH) dependent. In this study, we measured serum IGF-I, IGFBP-3 and 150 kDa levels in sera of growth hormone deficient children(GHD) before and after GH treatment respectively to clarify the utility of these factors as a diagnostic marker for GHD and to observe the alterations of these factors according to GH treatment. METHODS: Measurement of serum IGF-I, IGFBP-3 and 150 kDa complex were performed in 10 children with complete growth hormonr deficiency(cGHD), in 6 children with partial growth hormone deficiency(pGHD) and in 10 normal healthy subjects. Serum IGF-I was measured by radioimmunoassay (RIA). IGF-I was seperated from IGFBPs by Sephadex G-50 acid chromatography. Serum IGFBP-3 was assessed by Western ligand blot(WLB) analysis as described by Hossenlopp with minor modifications. To evaluate alterations of different molecular size classes of IGF-BP complexes according to GH treatment, WLB was done after neutral size-exclusion chromatography using Sephacryl S-200. RESULTS: 1) The serum IGF-I level in children with GHD was significantly lower than that of control subjects(96.2+/-40.1 ng/ml vs 147.5+/-37.9 ng/ml)(p<0.01). 2) The serum IGF-I level in children with cGHD was significantly lower than that of normal subjects (p<0.01). But four of the 10 children with cGHD the IGF-I levels were distributed within the range of -2 S.D.. The serum IGF-I level in children with pGHD was also lower than that of normal subjects but there was no statistical significance between two groups(P>0.05). 3) The serum IGFBP-3 level is markedly decreased in 9 of 10 children with cGHD, but only in 2 of 6 children with pGHD which was measured by WLB method. 4) The serum IGF-I level after GH treatment was increased significantly in children with GHD(138.7+/-49.2 ng/ml vs 78.7+/-23.4 ng/ml)(p<0.01). The serum IGFBP-3 level was also increased after GH treatment as similar pattern. 5) The marked decrement of serum IGFBP-3 level in children with cGHD was explained as the result of decline in the 150 kDa IGFBP complex, and after GH treatment 150 kDa complex was increased; in the 150 kDa IGFBP complex, free IGF-I binding sites were increased. CONCLUSIONS: The serum levels of IGF-I, IGFBP-3 and 150 kDa complex in children with cGHD were decreased significantly, but in children with pGHD these changes were not observed as prominant as cGHD. These findings suggest that the measurments of serum IGF-I, IGFBP-3 level may be useful not only in the diagnosis of GHD but also differentiate cGHD from pGHD and the serum IGFBP-3 level may be more sensitive for diagnosing GHD even though each test by itself has a limited diagnostic accuracy as a single test.
Binding Sites ; Child* ; Chromatography ; Diagnosis ; Growth Hormone* ; Humans ; Insulin* ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Radioimmunoassay ; Somatomedins

PURPOSE:Insulin-like growth factors, IGF- I and IGF-II, are proteins that promote cellular growth and differentiation of the various organs including the kidney. These peptides circulate in serum bound to specific carrier proteins, called IGF binding proteins(IGFBPs). The IGFs are produced in most organs but liver is believed to be the principal source of circulating IGF-I. We studied the correlation of serum IGF-I and IGFBP-2 pattern with aging. METHODS:Sera were collected from 320 healthy population who were grouped according to age. IGF-I was seperated from IGFBPs by Sephadex G-50 acid chromatography. We measured serum IGF-I and IGFBP-2 by using radioimmuno-assay (RIA) and immunoradiometric assay (IRMA) respectively. RESULTS:Serum IGF-I levels were quite low in early childhood, rising slowly and reaching a peak during puberty and a significant decline(P<00.01) during adulthood. The age-dependent pattern of serum IGFBP-2 levels shows a pattern opposite to that of IGF-I which are high at birth, decline by late puberty and increase again with aging. CONCLUSION: Our results demonstrate the alteration of serum IGF-I and IGFBP- 2 pattern with aging. These data suggests that when these tests are performed in the clinic, their interpretation should be based upon age specific criteria.
Adolescent ; Aging* ; Carrier Proteins ; Chromatography ; Humans ; Immunoradiometric Assay ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins ; Kidney ; Liver ; Parturition ; Peptides ; Puberty

OBJECTIVE: To evaluate the clinical efficacy of serum insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-3 (IGFBP-3) levels in predicting the prognosis of in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: In 84 patients undergoing IVF-ET, serum levels of IGF-I , IGF-II, and IGFBP-3 were measured using immunoradiometric assay (IRMA) before the gonadotropin administration and on the hCG day of controlled ovarian hyperstimulation (COH). Serum levels of IGFs and IGFBP-3, and the outcomes of IVF-ET were retrospectively analyzed and compared between the pregnant (n=18) and nonpregnant (n=66) groups. RESULTS: There were no significant differences in the outcomes of COH such as total dosage of gonadotropins used, duration of COH, serum estradiol (E2) level on the hCG day, numbers of oocytes retrieved and fertilized, and number of embryos transferred between the pregnant and nonpregnant groups. No differences were found in serum levels of IGF- I , IGF-II, and IGFBP-3, and their ratios before the gonadotropin administration and on the hCG day of COH. Basal serum level of IGF-II was lower with the borderline significance in the pregnant group (796.9+/-159.6 vs. 908.9+/-338.9 ng/ml, p=0.056). The ratio of change in IGF-I to that of IGF-II was significantly higher in the pregnant group (0.066+/-0.489 vs. -0.582+/-2.091, p=0.045). CONCLUSION: Even though basal serum level of IGF-II was lower and the ratio of changes in IGF-I to IGF-II was higher in the pregnant group, serum levels of IGF-I , IGF-II, and IGFBP-3 do not seem to predict the prognosis of IVF-ET. Further investigations are necessary in a larger group of patients to elucidate the clinical efficacy of serum IGFs and IGFBPs levels in predicting the prognosis of IVF-ET.
Embryo Transfer* ; Embryonic Structures* ; Estradiol ; Fertilization in Vitro* ; Gonadotropins ; Humans ; Immunoradiometric Assay ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II* ; Oocytes ; Prognosis* ; Retrospective Studies

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.
Age of Onset ; Child* ; Diabetes Mellitus, Type 1* ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins* ; Male

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.
Age of Onset ; Child* ; Diabetes Mellitus, Type 1* ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins* ; Male

Localized fibrous tumor of the pleura is rare, slowly growing, benign tumor. Most of these tumors clinically behave asymptomatically, although tumor-associated hypoglycemia occurs in a few cases and lead to hypoglycemic coma. Laboratory investigations show elevation of IGF-II with a 2-3 times higher effect on the blood glucose level than insulin. Surgical resection of the tumor is recommended. We report on the case of a 81-year-old man, who complained of hypoglycemic episodes. Diagnostic evaluation showed a fibrous tumor of pleura attached to the right diaphragm.
Aged, 80 and over ; Blood Glucose ; Coma ; Diaphragm ; Humans ; Hypoglycemia* ; Insulin ; Insulin-Like Growth Factor II ; Pleura*

Mesenchymal tumors including hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor (IGF) type II precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin like actions. In addition to increased IGF-II production, IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. The authors of this article diagnosed non-islet cell tumor hypoglycemia from an 81-year-old male patient suffering from repetitive fasting hypoglycemia while he has not received any treatment for pulmonary hemangiopericytoma diagnosed in the past. Moreover, this topic is getting reported as the authors have experienced a significant improvement of catamnesis by a treatment with glucocorticoid.
Aged, 80 and over ; Biological Availability ; Carrier Proteins ; Hemangiopericytoma ; Humans ; Hypoglycemia* ; Insulin ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Male ; Receptor, IGF Type 1 ; Receptor, Insulin

Since its discovery in 1921, insulin has been considered to be the most important hormone in the regulation of glucose and fat metabolism. In recent years, studies have revealed that besides metabolism regulation, insulin can also act as a growth factor like hormone in regulating multiple processes and various cellular activities in the process of wound healing. This review summarizes the role of insulin in wound healing and its underlying mechanism.
Glucose ; metabolism ; Growth Hormone ; metabolism ; physiology ; Humans ; Insulin ; physiology ; Insulin-Like Growth Factor I ; physiology ; Insulin-Like Growth Factor II ; physiology ; Wound Healing ; physiology

PURPOSE: PTEN/MMAC1, a novel tumor suppressor gene, is mutated in a variety of advanced and metastatic cancers. It acts as a phosphatase, and thereby, regulates the PI-3 kinase/Akt pathway. In this study, we examined to evaluate the new function of anti-tumor effects of PTEN/MMAC1 through the regulation of the IGFs-IGFBPs in gastric cancer cells. METHODS: PTEN/MMAC1 was expressed in an adenovirus-mediated gene delivery system and introduced into gastric cancer cells(SNU-484 & SNU-668) in vitro. The effect of cell growth and the expression of IGFs and IGFBPs after Ad/PTEN infection was analyzed by MTT assay, RT-PCR and Western immunoblot. RESULTS: Ad/PTEN infected cells were inhibited in cell growth compared with moak cells and Ad/ LacZ infected cells. Overexpression of PTEN/MMAC1 induced decrease in expression of IGF-I, -II and IGF-I receptors which are known as growth prompt molecules in a variety of cancers. Of the six IGFBPs, the expressions of IGFBP-4 and IGFBP-6 were decreased in Ad/PTEN infected cells. In contrast, IGFBP-3 expression was markedly increased by up to 3-fold in Ad/PTEN infected cells. Overexpression of PTEN/MMAC1 inhibited the activation of Akt/PKB pathway, but had no effect on the MAPK pathway. CONCLUSION: These findings suggest that the tumor suppressor function of PTEN/MMAC1 is, at least in part, mediated through the down-regulation of IGF-I abd IGF-II, and up-regulation of IGFBP-3 in gastric cancer cells by the inhibition of PI-3 kinase pathway.
Blotting, Western ; Down-Regulation ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Protein 6 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases ; Receptor, IGF Type 1 ; Stomach Neoplasms ; Up-Regulation