IGF-II gene promoter P3 methylation in salivary pleomorphic adenoma / 实用口腔医学杂志

Objective:To detect the methylation status of insulin-like growth factor Ⅱ(IGF-Ⅱ)gene promoter P3 in salivary pleo-morphic adenoma(SPA).Methods:The methylation of IGF-Ⅱ gene promtor P3 was examined in 26 cases of salivary pleomorphic adenoma with adjacent normal salivary gland tissues,1 0 cases of salivary gland malignant tumor (except malignant pleomorphic ade-noma)and 1 0 cases of normal salivary gland tissue by nested methylation specific polymerase chainreaction(nMSP),1 0 samples(3 SPA and controls,2 malignance and controls)were examined by pyrosequencing.Results:9 out off the 26 SPA showed lower level methylation oevel of IGF-II gene promoter P3.Normal salivary gland and salivary gland malignant tumor tissue did not.Conclusion:IGF-II gene promoter P3 with low level of methylation may play a role in the development of SPA.

Regulation of hypoxia-inducible factor-1α (HIF-1α) expression by interleukin-1β (IL-1 β), insulin-like growth factors I (IGF-I) and II (IGF-II) in human osteoarthritic chondrocytes

OBJECTIVE: Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothesize that Hypoxia Inducible Factor-1 alpha (HIF-1α) can regulate cytokines (catabolic action) and/or growth factors (anabolic action) in osteoarthritis. The purpose of this study was to investigate the modulation of HIF-1α in human osteoarthritic chondrocytes by interleukin-1 beta (IL-1β) and insulin-like growth factors I (IGF-I) and II (IGF-II) and to determine the involvement of the phosphatidylinositol-3kinase (PI-3K) pathway in this process. METHODS: Human osteroarthritic chondrocytes were stimulated with IL-1β, IGF-I and IGF-II and LY294002, a specific inhibitor of PI-3K. Nuclear protein levels and gene expression were analyzed by western blot and quantitative reverse transcription-polymerase chain reaction analyses, respectively. RESULTS: HIF-1α expression was upregulated by IL-1β at the protein level but not at the gene level. IGF-I treatment resulted in increases in both the protein and mRNA levels of HIF-1α , whereas IGF-II had no effect on its expression. However, all of these stimuli exploited the PI-3K pathway. CONCLUSION: IL-1β upregulated the levels of HIF-1α protein post-transcriptionally, whereas IGF-I increased HIF-1α at the transcript level. In contrast, IGF-II did not affect the protein or gene expression levels of HIF-1α . Furthermore, all of the tested stimuli exploited the PI-3K pathway to some degree. Based on these findings, we are able to suggest that Hypoxia inducible Factor-1 exhibits protective activity in chondrocytes during osteoarthritis.

Igf-ii y la gonddotropina coriónica regulan la roliferación, migración e invassión de células de trofoblasto humano / IGF-II and Chorionic Gonadotropin Regulate Proliferation, Migration and Invasion of Human Trophoblast Cells

Son conocidas las propiedades del factor de crecimiento similar a la insulina tipo II (IGF-II) y de la hormona gonadotropina coriónica (hCG) en implantación y migración trofoblástica; sin embargo, los mecanismos moleculares a través de los cuales ejercen sus efectos no están completamente caracterizados. El objetivo de este estudio fue establecer la interacción potencial entre los efectos funcionales de hCG e IGF-II en la regulación de la proliferación, migración e invasión trofoblástica. Utilizando la línea celular HTR-8/SVneo de trofoblasto extravelloso se estableció que IGF-II promueve la proliferación celular y de manera novedosa se demostró que hCG, a concentraciones elevadas, es capaz de estimular la proliferación trofoblástica, a través de un mecanismo independiente al empleado por IGF-II. En contraste, la capacidad invasiva del trofoblasto fue regulada por IGF-II y hCG, planteando la existencia de un efecto aditivo en sus acciones. En conclusión, nuestros resultados demuestran el papel de hCG e IGF-II en la regulación de la proliferación e invasión del trofoblasto y plantean la existencia de interacciones a nivel de sus acciones biológicas, contribuyendo a un mejor entendimiento de la biología del trofoblasto y sus patologías.

Both IGF-II and chorionic gonadotropin (hCG) are important regulators of human trophoblast migration and implantation; however the molecular mechanisms are not fully understood. The purpose of this study was to determine the potential cross-talk between functional effects of hCG and IGF-II in the regulation of trophoblast proliferation, migration and invasion. Using the HTR-8/SVneo trophobast cell line we found that IGF-II stimulates cell proliferation and, for the first time we demonstrate that hCG at high doses is able to promote trophoblast proliferation through a mechanism independent of IGF-II. In contrast, trophoblast invasiveness was regulated by both IGF-II and hCG and an additive effect between the two hormones was observed. In conclusion, our results demonstrate cross-talk between the biological activities of IGF-II and hCG in the regulation of trophoblast invasiveness and contribute to a better understanding of the trophoblast biology and pathology.

A Case of Gastrointestinal Stromal Tumor with Recurrent Hypoglycemia

Non-islet cell tumor induced hypoglycemia (NICTH) is attributable to overproduction of insulin-like growth factor-II (IGF-II) by solid tumors, and these tumors usually originate from mesenchymal or epithelial cells. Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor and most commonly find in the gastrointestinal tract. It is usually expresses the CD117 (stem cell factor receptor, c-kit) detected by immunohistochemistry. Hypoglycemia associated with GIST is very rare and this has not yet been reported in Korea. A 72-year-old man was hospitalized due to frequent episodes of confusion. It was observed that non-hyperinsulinemic hypoglycemia, an elevated serum IGF-II level and a huge liver mass. The histology of liver mass showed c-kit (CD117) positivity, which was consistent with GIST, but it was surgically unresectable. He was treated with imatinib mesylate. Although he recieved palliative treatment, he still experienced intermittent fasting hypoglycemia. After 2 months, the serum IGF-II level was even higher than before. We changed imatinib mesylate to sunitinib malate and performed radiotherapy on the liver mass. Although the change of the liver mass was not significant, he did not suffer from hypoglycemia for three months afterwards.

RELACIÓN DE LA EXPRESIÓN DE mARN DE LAS METALOPROTEINASAS 2 Y 9 Y EL INHIBIDOR TIMP-1 EN MOLA HIDATIDIFORME COMPLETA / RELATIONSHIP BETWEEN METALLOPROTEINASES 2 AND 9 AND TIMP-1 INHIBITOR mRNA EXPRESSION IN HYDATIDIFORME MOLE / RELAÇÃO DA EXPRESSÃO DE mRNA DAS METALOPROTEINASAS 2 E 9 E DO INHIBIDOR TIMP-1 NA MOLA HIDATIDIFORME COMPLETA

Durante el comienzo de la gestación el factor de crecimiento similar a la insulina tipo II (IGF-II) se expresa abundantemente en la placenta y podría regular el comportamiento invasivo de las células trofoblásticas. La habilidad invasiva dependerá también de la capacidad de secretar metaloproteinasas (MMPs), cuya expresión anormal contribuye a varios procesos patológicos. En la Enfermedad Trofoblástica Gestacional (ETG) estos factores podrían estar desregulados, así la mola hidatidiforme completa (MHC) conduce a la formación del coriocarcinoma, que es un tumor invasivo y metastásico. El objetivo de este estudio fue investigar la relación entre los niveles de mARN de IGF-II, MMP-2, MMP-9 y TIMP-1, por la técnica de RT-PCR, en tejidos de mola hidatidiforme vs. placentas de primer trimestre. La actividad de las MMPs se evaluó usando el ensayo de zimografía, encontrando que en MHC ésta se incrementa, lo cual podría relacionar la malignización del trofoblasto con el incremento en su capacidad invasiva. La expresión elevada de IGF-II en esta patología, también podría estar asociada con el incremento en la actividad de estas MMPs. Una mayor relación entre la expresión de mARNde MMP-9/TIMP-1 en la mola hidatidiforme completa se sugiere como predictor de malignización del tejido trofoblástico .

At the beginning of gestation the Insulin Like Growth Factor II (IGF-II) is highly expressed in placenta and it could regulate the invasive behavior of trophoblastic cells. This invasive ability depends on its capability to secret metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), abnormal expression of which could contribute to several pathological processes.In the Gestational Trophoblastic Diseases (GTD) these factors could be unregulated, in this way complete hydatidiforme mole (CHM) produces the choriocarcinoma which is an invasive and metastasic tumor. The aim of this study was to investigate the relationship between IGF-II, MMP-2, MMP-9 and TIMP-1 mRNA levels by RT-PCR technique, in hydatidiform mole tissues vs. first normal trimester placentas. MMPs activity was evaluated using zimography assay finding that in CHM this is increased, which could relate trophoblast malignization with an increased invasive capability. The higher IGF-II mRNA expression in this pathology could, also, be associated with increased MMPs activity. A higher MMP-9/ TIMP-1 mRNA expression ratio in CHM is suggested as a predictor of trophoblastic tissue malignization .

No início da gestação o fator de crescimento semelhante à insulina tipo II (IGF-II) é altamente expresso na placenta e poderia regular o comportamento invasivo das células trofoblásticas. Esta habilidade invasiva também depende da sua capacidade de produzir metaloproteinasas (MMP) e inibidores das mesmas (TIMP), expressão anormal da qual poderia contribuir em vários processos patológicos. Nas Doenças Trofoblásticas da Gestação (Gestational Trophoblastic Disease, ETG) estes fatores poderiam ser desregulados; deste modo a Mola Hidatidiforme Completa (MHC) produz coriocarcinoma que é um tumor invasivo e metastásico. O objetivo deste estudo era pesquisar a relação entre os níveis de mRNA do IGF-II, MMP-2, MMP-9 e TIMP-1, através da técnica de RT-PCR em tecidoos da MHC vs. placenta do primeiro semestre. Atividade das MMP foram avaliadas pelo ensaio de zimografia achando que em MHC aumenta; isto poderia relacionar o incremento do malignidade do trofoblasto com uma capacidade invasiva aumentada. A expressão mais alta do IGF-II nesta patologia pode também estar associada com atividade aumentada destas MMP. Uma relação aumentada da expressão do mRNA de MMP-9/TIMP-1 na MHC é sugerida como um preditor do incremento da malignidade do tecido trofoblástico .

A Case of Non-islet Cell Tumor Hypoglycemia / 대한내분비학회지

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.

IGF-I and -II production during menstrual cycle / 대한산부인과학회지

OBJECTIVE: We designed this study to understand the physiologic effects and secretory pattern of IGF-I and IGF-II in human serum and changes in expression of IGF-I and IGF-II in human ovarian tissues during menstrual cycle, and to know which one is more important on human ovarian function between IGF-I and IGF-II, related to FSH, LH and estradiol. METHODS: IGF-I, IGF-II, FSH, LH and estradiol levels were measured in 80 serum samples by ELISA from normal reproductive women. We also examined the immunohistochemical staining of the IGF-I and IGF-II in the ovarian tissues of 14 normal reproductive women. The mean age was 35.6+/-9.15 years-old, ranged from 20 to 45. The average menstrual cycle was 27 to 29 days. RESULTS: 1. The average serum concentration of IGF-I was 204.43+/-50.92 ng/mL, and that of IGF-II was 1381.56+/-292.56 ng/mL. 2. The regular pattern or relationship on serum IGF-I and IGF-II concentrations were not observed (P=0.19). 3. To cross-correlation of serum concentrations of FSH, LH, estradiol and IGF-I, IGF-II, IGF-II was thought to effect on human ovarian menstrual cycles, affected by action of FSH (P=0.048). 4. In the normal reproductive ovaries, we observed immunohistochemical staining for IGF-I in primary, secondary, mature follicle, corpus luteum and stroma, but not in corpus albicans. 5. In the normal reproductive ovaries, we observed immunohistochemical staining for IGF-II in primary, secondary, mature follicle, and corpus luteum but not in corpus albicans and stroma. 6. Stronger immunohistochemical staining was observed in ovaries for IGF-II, rather than IGF-I. CONCLUSION: IGF-I and IGF-II were produced by ovarian tissues, and participated in ovarian folliculogenesis according to menstrual cycles by paracrine, autocrine functions. IGF-II, rather than IGF-I, was thought to effect greater on human ovarian menstrual cycles, affected by action of FSH.

Insulin-like Growth Factor-II (IGF-II) Induces Vascular Endothelial Growth Factor (VEGF) Expression through IGFR-1 and ERK1/2 Activation in Psoriasis / 대한피부과학회지

BACKGROUND: Psoriasis is a chronic relapsing and angiogenic skin disease characterized by variable clinical features. But the pathogenetic process resulting in vascular morphological changes remains to be proven. It is reported that the potent angiogenic factor VEGF is overexpressed in psoriatic epidermis and the level of IGF-II is significantly elevated in tissue fluid and serum of the psoriatic lesion. OBJECTIVE AND METHOD: To find the mechanism of VEGF induction in pathogenesis of psoriasis, we adopt IGF-II as a paracrine inducer of VEGF in psoriasis. To investigate the signaling pathway of IGF-II-induced VEGF, we determined ERK1/2 activity in IGF-II-treated psoriatic cells. RESULT: In this report, we demonstrated that IGF-II induced the expression of VEGF in lesional keratinocytes of psoriasis. And IGF-II stimulated the expression of its receptor, IGFR-I in psoriatic cells. Treatment of anti-IGFR-I neutralizing antibody diminished VEGF mRNA level induced by IGF-II, indicating that VEGF induction by IGF-II may be mediated through IGFR-I. By the treatment of PD98059, specific inhibitor of upstream ERK activator MAP kinase/ERK kinase (MEK), the expression of VEGF induced by IGF-II was dramatically reduced. CONCLUSION: Taken together, these results suggest that IGF-II might regulate angiogenesis by the induction of VEGF through the MAP kinase pathway mediated by IGFR-I in the lesion of psoriasis.

Alteration of Growth Factor Expression after Acute Ischemic Renal Injury

PURPOSE: Regeneration and repair after ischemic renal injury appears to be modulated by circulating or locally produced growth factors. This study examined the changes of serum insulin like growth factor(IGF-I) and renal expression of IGF-I and II, vascular endothelial growth factor(VEGF), transforming growth factor-beta(TGF-beta), and connective tissue growth factor(CTGF) during the active regeneration period after acute ischemic injury. METHODS: Sera and kidney tissue samples(whole kidney, cortex, outer medullae and inner medullae) were obtained before and after one, three, five and seven days of 40 minutes bilateral renal pedicle clamping. Acute renal failure was assessed by measuring the concentration of serum creatinine. Serum IGF-I level was measured by radioimmunoassay. The mRNA expression in kidney was measured by RT-PCR. The distribution of IGF-I and CTGF was detected by immunohistochemistry. RESULTS: Serum IGF-I concentration after one day following acute ischemic renal injury was significantly decreased compared to preischemic value. The mRNA levels of IGF-I, IGF-II, TGF-beta1 and VEGF in whole kidney were temporally decreased on day one of ischemic injury. IGF-I and IGF-II expressions in outer medullae were significantly decreased on day one after ischemic injury. TGF- beta, CTGF and VEGF expressions were markedly decreased in medullae after one day of ischemic injury compared to other kidney sections. IGF-I was markedly decreased in cortical tubules on day one of uremic rat. CTGF was markedly increased on tubule within three days of ischemic injury. CONCLUSION: These findings suggest that IGFs, TGF-beta and CTGF may involve in the pathogenesis or the recovery from acute ischemic renal injury.

The Correlation of Ovarian Follicular Concentrations of IGF-II, IGFBP-1, and 3 between Cumulative Embryo Score in Patients Undergoing IVF-ET / 대한산부인과학회잡지

OBJECTIVE: To investigate the correlation between the concentrations of insulin-like growth factor-II (IGF-II), insulin-like growth factor binding protein-1, 3 (IGFBP-1, 3) in the follicular fluid and the cumulative embryo score (CES) in the patient who underwent in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: A total of 21 cycles of 18 patients which underwent IVF-ET cycle after controlled ovarian hyperstimulation (COH) were included in this study. Using immunoradiometric assay (IRMA), we measured the concentrations of IGF-II, IGFBP-1, 3 in the follicular fluid. The patients were grouped into the pregnant and non-pregnant group. The concentrations of IGF-II, IGFBP-1, 3 in the follicular fluid were compared between the two groups and the correlations of the follicular concentrations of IGF-II, IGFBP-1, 3 and cumulative embryo score were evaluated. Results were analyzed with Mann-Whitney U test and Spearman's rank correlation coefficient and statistical significance was defined as p<0.05. RESULTS: There were no statistical significance in the follicular concentrations of IGF-II, IGFBP-1, 3 between the pregnant group and non-pregnant group. There were signifiant correlation between the follicular concentration of IGF-II and cumulative embryo score (p=0.001). There might be correlations between the follicular concentration of IGFBP-3, and free IGF-II and cumulative embryo score (p=0.053, p=0.056, respectively). CONCLUSION: The follicular IGF-II and free IGF-II might have an influence to development of good- quality embryos in patients undergoing IVF-ET.

Clinical Efficacy of Serum Insulin-like Growth Factor- I (IGF-I), IGF-II, and IGF Binding Protein-3 (IGFBP-3) in Predicting the Prognosis of In Vitro Fertilization and Embryo Transfer / 대한산부인과학회잡지

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.

Study on the Expression of Insulin-like Growth Factor II (IGF- II) in Hepatocellular Carcinoma Cells and Developing Rat Embryos / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The insulin-like growth factor II (IGF-II) gene expresses a family of transcripts in embryonic/fetal tissue, and also highly was expressed during hepatocellular carcinogenesis. In this study, we showed that IGF-II mRNA and protein levels are detected in rat embryo, HepG2 human hepatoma cells and Chang liver cells. MATERIALS AND METHODS: This study included sections of rat embryos 7~17 days post coitum (d.p.c), HepG2 cells and Chang liver cells. Using immunohistochemistry, Northern blotting and Western blotting, we observed the expression of IGF-II in the rat embryo, HepG2 cells and Chang liver cells. RESULTS: We localized IGF-II gene products in sections of rat embryo 7~17 d.p.c by performing immunohistochemistry. The IGF-II was mainly expressed in the proximal endoderm and ectoplacental cone between 7 and 9 d.p.c. At 10 d.p.c. the expression was localized at the heart primodium as well as the proximal endoderm, and at 11 d.p.c. the IGF-II was expressed in the liver and heart. After 12 d.p.c. and 14 d.p.c., the expression was also detected in the brain, muscle and bone, and head mesenchyme, respectively. While the expression of IGF-II protein was not detected in the normal adult liver, intense staining was detected in the heart, liver and choroids plexus at 17 d.p.c. CONCLUSION: These results suggest that IGF-II may act as an oncofetal protein during hepatocellular carcinogenesis and embryogenesis.

Neurotoxic Effect of Streptozotocin and Neuroprotective Effect of Insulin Growth Factor-II to the Cultured Mouse Schwann Cells / 대한이비인후과학회지

BACKGROUND: The sensorineural hearing loss due to diabetes is progressive and bilateral, and predominantly occurs in the old, although its accurate pathogenesis is still unknown. Objectives: The purpose of this study is to clarify the neurotoxic effect of streptozotocin (STZ) and the neuroprotective effect of insulin-like growth factor-II(IGF-II) on the cultured Schwann cells of cohlear nerve. MATERIALS AND METHODS: MTT assays were performed on cultured mouse Schwann cells which were treated with various concentrations of STZ for 24 hours, and the neuroprotective effect of IGF-II against STZ-induced neurotoxicity were also examined. RESULTS: 1) MTT50 value was the concentration of 40 pM STZ (highly toxic : MTT50<100 pM), 2) Cell viability of cultured mouse Schwann cells treated with STZ markedly decreased in a dose-dependent manner. CONCLUSION: It is suggested that STZ induces a severe toxic effect on cultured Schwann cells of mouse, and selective neurotrophic factors such as IGF-II are very effective in preventing the neurotoxicity induced by STZ.

Neurotrophins and IGFs Attenuated Haloperidol-Induced Neuronal Apoptosis in Mouse Cortical Cell Cultures / 신경정신의학

OBJECTIVES: We examined the effects of neurotrophins and insulin-like growth factors on cell death induced by haloperidol, a typical anti-psychotic agent. METHOD: Neocortices from 14- or 15-daysold fetal mice for neuron-glia co-cultures were used for this experiment. RESULT: Twenty-four hours treatment of mouse cortical cell cultures with 30 M haloperidol-induced wide spread neuronal apoptosis characterized by cell body shrinkage, DNA fragmentation and condensation. Concurrent treatment with growth factors, BDNF, NT4/5, IGF-I and IGF-II, protect the neurons from the haloperidol-induced neuronal apoptosis(HINA) in a dose dependent manner(10-100ng/ml). CONCLUSION: The present study suggests the possibility that haloperidol toxicity can be hampered with growth factors. Further study about the mechanism underlying the protective capacity of the growth factors on HINA may lead to the development of the new protective strategy for tardive dyskinesia.

Serum IGF-I, IGF-II and IGFBP-3 levels in children with isolated growth hormone deficiencies and panhypopituitarism.

Serum IGF-I,IGF-II and IGFBP-3 levels were measured by radio-immunometric assay in 24 children, 16 with isolated growth hormone deficiencies (GHD) and 8 with panhypopituitarism. AII serum parameters were significantly lower in panhypopituitarism than in isolated GHD. Serum IGF-I levels were lower than the normal range in 50 percent of the patients. However, 66.7 percent of isolated GHD children older than 10 years had serum IGF-I levels lower than the normal range. AII isolated GHD children had serum IGFBP-3 levels lower than the 50th percentile or mean of normal range. Combined IGF-I and IGF-II levels had no more advantage than IGF-L levels in the diagnosis of isolated GHD. Serum IGFII levels were lower than normal range in 87.5 percent. In conclusion, serum IGFBP-3 measurement is useful than IGF-I in all age groups. Low serum IGF-II levels and panhypopituitarism were demonstrated in this study.

A Case of non-islet Cell Tumor Hypoglycemia Due to Gepatoma-increased serum subfraction of big insulin-like growth factor II / 대한내분비학회지

Hypoglycemia due to non-islet cell tumor is usually associated with hypersecretion of big insulin-like growth factor II (IGF-II). This big IGF-II cannot form ternary IGF complex, and is biologically more active in peripheral tissue, inducing increased glucose utilization and hypoglycemia. A 57-year-old man developed severe hypoglycemia due to hepatocellular carcinoma. To control hypoglycemia, the patient required continuous glucose infusion. The circulating levels of cortisol and free T4 were in the normal range. The plasma levels of insulin, C-peptide, IGF-I, IGF binding protein-3 (IGFBP-3), and total IGF-II levels were decreased. Radioimmunoassay of IGF-II revealed that big IGF-II immunoreactivity markedly increased compared to that of normal control. In this patient, it was strongly suggested that big IGF-II might be a cause of severe intractable hypoglycemia.

Characteristics of Serum Insulin-like Growth Factor ( IGF ) and IGF-Bindign Protein-3 during Pregnancy / 대한내분비학회지

BACKGROUND: Pregnancy in human and rodents is associated with dramatic matemal metabolic changes. Insulin-like growth factors (IGFs) are mitogenic peptides that are essential for fetal and maternal tissue growth during pregnancy. They circulate complexed primarily with a serum IGF-binding protein (IGFBP-3) which regulates the availability of the IGFs to their specific target tissues. METHODS: To examine the changes of IGFs and IGFB-3 during pregnancy, we measured serum total IGF-I, free IGF-I, IGF-II and IGFBP-3 by using specific radioimmunoassay, immunoradio-metric assay, western ligand blot and western immunoblot. Blood samples were obtained from 88 pregnant women between 6-40 weeks gestation. RESULTS: While serum IGF-I levels increased up to 50% in late pregnancy, serum IGF-II levels remained unchanged. However, serum free IGF-I levels were significantly higher during pregnancy than in nonpregnancy. Western ligand blot analysis revealed that IGFBP-3 in pregnancy serum was significantly decreased at 6 weeks of gestation, continued decreased level until term, and returned to a nonpregnant level by postpartum 10 day. Serum IGFBP-3 profiles in Western immunoblot analysis revealed that 30 kDa fragments of IGFBP-3 were detectable in pregnancy serum but not in nonpregnancy serum. In contrast, serum IGFBP-3 levels using radioimmunoassay was significantly increased in late pregnancy. CONCLUSIONS: 1) serum IGF-I was significantly elevated in late pregnancy 2) serum IGF-II was not significantly changed 3) free IGF-I significantly elevated throughout gestation 4) intact IGFBP-3 was markedly reduced after 6 weeks of gestation.

Factores de crecimiento II: Factores insulinoides de crecimiento / Growth factors II: insuline-like growth binging proteins (GFBPs)

Se revisan los Factores Insulinoides de Crecimiento, también denominados "Factores de Crecimiento Similares a la Insulina", sobre los cuales se dispone de abundante información. Se sintetizan conocimientos recientes sobre dichos factores con énfasis en los siguientes aspectos: estructura bioquímica, concentraciones y sus cambios en los líquidos biológicos, proteínas fijadoras, receptores, mecanismos de acción y efectos biológicos

This review summarizes recent knowledge concerning Insulin.like growth factors I and II, with emphasis on their biochemical structure, concentrations, binding proteins, receptors, mechanisms of action, biological effects, and alterations of their concentrations in biological fluids