• 제목/요약/키워드: Insulin-like growth factor I (IGF-I)

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IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down-regulation of TLR4 Signaling

  • Lee, Won-Jun
    • IMMUNE NETWORK
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    • 제11권4호
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    • pp.223-226
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    • 2011
  • Although exercise-induced growth factors such as Insulin-like growth factor-I (IGF-I) are known to affect various aspects of physiology in skeletal muscle cells, the molecular mechanism by which IGF-I modulates anti-inflammatory effects in these cells is presently unknown. Here, we showed that IGF-I stimulation suppresses the expression of toll-like receptor 4 (TLR4), a key innate immune receptor. A pharmacological inhibitor study further showed that PI3K/Akt signaling pathway is required for IGF-I-mediated negative regulation of TLR4 expression. Furthermore, IGF-I treatment reduced the expression of various NF-${\kappa}B$-target genes such as TNF-${\alpha}$ and IL-6. Taken together, these findings indicate that the anti-inflammatory effect of exercise may be due, at least in part, to IGF-I-induced suppression of TLR4 and subsequent downregulation of the TLR4-dependent inflammatory signaling pathway.

붕어육의 단백질 열수추출물이 흰쥐의 혈청중 Insulin-like Growth Factor-I(IGF-I)과 IGF-Binding Proteins에 미치는 영향 (Effects of Carassius carassius Hot-Water Extracts on Serum Insulin-like Growth Factor-I(IGF-I) and IGF-Binding Proteins in Rats)

  • 남택정;권미진;류홍수;김경숙;변재형
    • 한국식품영양과학회지
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    • 제28권3호
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    • pp.685-690
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    • 1999
  • The insulin like growth factors(IGFs) are bound to several binding proteins(IGFBPs) that appear to regulate IGF transfort, receptor binding, and its action. The concentrations of these peptides are regulated by quantity and nutritional quality of dietary proteins. The aim of this study was to compare the effects of two diets, which differed in their protein source, Carassius carassius(CC), Carassius carassius hot water extract(CCHE), for 4 weeks. Body weight was significantly increased in the CC group(74.14$\pm$12.00 to 266.31$\pm$36.62g; p<0.01). Likewise, IGF I concentration of CC group(101.76$\pm$15.90 ng/ml) was significantly higher than that of CCHE group(38.50$\pm$ 11.20ng/ml; p<0.05). By western immunoblot analysis, especially IGFBP 1, 2 levels are increased, whereas IGFBP 3 level was de creased in CCHE group. After extraction of browning material from each samples, the extractive was filtered and absorbance at 420nm was measured. The absorbance of CCHE group was significantly higher than that of CC group. These results suggest that IGF I can be employed as an index of protein metabolism, particulary as a simple index in the assessing the status of protein nutrition.

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Mesangial 세포에서 고포도당에 의한 insulin-like growth factor의 분비조절기전에 관한 연구: cAMP와의 관련성 (The regulatory mechanism of insulin like growth factor secretion by high glucose in mesangial cell: involvement of cAMP)

  • 허정선;강창원;한호재;박수현
    • 대한수의학회지
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    • 제43권4호
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    • pp.563-571
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    • 2003
  • Dysfunction of mesangial cells has been contributed to the onset of diabetic nephropathy. Insulin like growth factors (IGFs) are also implicated in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion in the mesangial cells. Furthermore, the relationship between cAMP and high glucose on the secretion of IGFs was not elucidated. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. Glucose increased IGF-I secretion in a time- (>8 hr) and dose- (>15 mM) dependent manner (p<0.05). Stimulatory effect of high glucose on IGF-I secretion is predominantly observed in 25 mM glucose (high glucose), while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. High glucose also increased IGF-II secretion. The increase of IGF-I and IGF-II secretion is not mediated by osmotic effect, since mannitol and L-glucose did not affect IGF-I and IGF-II secretion. 8-Br-cAMP mimicked high glucose-induced secretion of IGF-I and IGF-II. High glucose-induced stimulation of IGF-I and IGF-II secretion was blocked not by pertussis toxin but by SQ 22536 (adenylate cyclase inhibitor). Rp-cAMP (cAMP antagonist), and myristoylated protein kinase A (PKA) inhibitor amide 14-22 (protein kinase A inhibitor). These results suggest that cAMP/PKA pathways independent of Gi protein may mediate high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. Indeed, glucose (>15 mM glucose) increased cAMP formation. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via cAMP/PKA pathway in mesangial cells.

Insulin-Like Growth Factor-I-Induced Androgen Receptor Activation Is Mediated by the PI3K/Akt Pathway in C2C12 Skeletal Muscle Cells

  • Lee, Won Jun
    • Molecules and Cells
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    • 제28권5호
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    • pp.495-499
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    • 2009
  • Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

사료의 단백질이 조피볼락 혈액중 Insulin-like growth factor-I (IGF-I) 및 IGF-binding protein-3에 미치는 영향 (Effects of Dietary Proteins on Serum Insulin-like Growth Factor-I (IGF-I) and IGF-Binding Protein-3 in Korean Rockfish, Sebastes schlegeli)

  • 남택정;권미진;이상민;박기영;김윤;박승렬;변재형
    • 한국수산과학회지
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    • 제34권5호
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    • pp.550-555
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    • 2001
  • 조피볼락을 실험어로 하여 사료 단백질의 함량과 단백질원을 달리하여 공급한 후 동물의 성장인자 중 하나인 Insulin-like growth factor-I (IGF-I)과 IGFBP-3의 혈중농도를 검토하였다. 사료 단백질의 함량이 $50\%\sim60\%$ 급여군에서 성장이 좋았고, 혈액중 IGF-I 농도도 높게 나타났다. 그리고 콘글루텐과 우모분 보다 질적으로 우수한 어분, 대두박분, 육분을 첨가한 사료로 사육한 조피볼락의 혈액중 IGF-I과 IGFBP-3가 높은 것으로 나타났으므로, 어류 단백질 대사수준을 파악하는 지표로 활용이 가능하였다.

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당뇨환자의 식사 전후에 따른 혈중 Insulin-like growth factor(IGF-I), IGF-II 및 Insulin-like growth factor binding proteins(IGFBP)-3의 변화 (Changes of Insulin-like Growth factor-I, II and IGF-Binding Protein-3 on Fasting and Postprandial state in Diabetes)

  • 허영란;강창원;차연수
    • 한국가정과학회지
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    • 제9권1호
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    • pp.81-88
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    • 2006
  • IGFs and IGFBPs have an important role in controlling glucose homeostasis. This study was conducted to investigate the changes of insulin-like growth factor(IGF)-I. IGF-II and IGF binding proteins (IGFBPs) on fasting and postprandial state in Korean diabetes, Twenty eight healthy subjects and fifty seven diabetic patients participated in this study. The healthy subjects were not knowingly suffered from any disease and were not receiving any medical treatment, and diabetic subjects were undergo medical treatment, continuously. Weight and height were measured and body mass index (BMI) was calculated as weight (kg) divided by the square of height (m2). Blood pressure was measured. Plasma lipid profiles were analyzed by enzymatic methods, plasma Insulin and glucose levels were measured in fasting and postprandial state, respectively. The levels of serum IGFs and IGFBP-3 were measured by radioimmunoassay (RIA). The levels of glucose and insulin were significantly higher in diabetes than normal subjects on fasting as well as postprandial state (p<0.0l). The levels of IGF-I was significantly lower in diabetes than normal subjects, however in postprandial state, there was no significant difference between diabetes and control subjects, The levels of IGF-II were significantly lower in diabetes than control subjects both fasting and postpradial state, The level of IGFBP-3 were not significantly different between diabetes and normal subjects. Fasting IGF-I, IGF-II and IGFBP-3 levels were positively correlated with those levels on postprandial state, fasting IGe levels of IGF-I levels were positively correlated with fasting insulin levels, and postprandial IGF-I levels were positively correlated with fasting glucose, postprandial insulin and postprandial insulin levels, plasma triglyceride levels were correlated with plasma triglyceride levels. The IGFBP-3 levels were not correlated with IGF components, glucose, insulin and plasma lipids, These results demonstrate that in diabetes, the components IGF-I/IGFBPs system were significantly correlated with plsma glucose and insulin levels both fasting and postprandial state.

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Insulin-like growth factor-I 유전자의 조직 특이적 발현에 대한 조절기전 (Regulatory Mechanism in Tissue-specific Expression of Insulin-like Growth Factor-I Gene)

  • 안미라
    • KSBB Journal
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    • 제18권4호
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    • pp.329-334
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    • 2003
  • Insulin-like growth factor-I (IGF-I) 유전자의 발현은 사람 및 쥐에서 두 개의 promoters (P1과 P2)로부터의 전사와 alternative RNA splicing 및 differential RNA polyadenylation과 같은 복잡한 기전들에 의하여 조절되는데 조직에 따라 성장호르몬을 포함한 여러 요소들이 관여하는 것으로 알려져 있다. 또한 사람의 IGF-I 유전자 exon 1의 upstream에 존재하는 P1에 hepatocyte nuclear factor l$\alpha$와 CAAT/enhancer-binding protein (C/EBP) isoform 들이 결합하여 조직 및 발달단계 특이한 발현에 중요한 역할을 할 것으로 제안되었지만, exon 1의 downstream sequence가 IGF-I 유전자의 조직 특이적 발현을 조절하는 지에 대하여는 연구되어 있지 않다. 연령이 다른 쥐의 간 및 뇌 조직에서 total RNA를 분리하고 solution hybridization/RNase protection 방법으로 분석하여 IGF-I 유전자의 발현이 태어난 후 간 조직에서는 점차적으로 증가하였지만 뇌조직에서는 감소하여 발달단계에 따라 조직 특이하게 발현되는 것을 확인하였다. IGF-I exon 1의 주요한 전사 개시점으로부터 아래쪽에 존재하는 C/EBP 결합부위를 포함하고 있는 cis-acting element에 해당하는 oligonucleotide들과 간 및 뇌조직에서 분리한 핵단백질들을 이용하여 DNA-결합 활성을 가진 분자량이 다른 C/EBP$\alpha$나 C/EBP$\beta$ 단백질들을 확인하였으며 southwestern 및 western immnoblotting 분석을 하여 간 조직의 핵 추출물에서는 42$^{C}$EBP$\alpha$/, 와 p38$^{C}$EBP$\alpha$/, p35$^{C}$EBP$\alpha$/, p38$^{C}$EBP$\beta$/, 그리고 p35$^{C}$EBP$\beta$/가 IGF-I exon 1 oligonucleotide와 복합체를 형성하고 뇌 조직에서는 p42$^{C}$EBP$\alpha$과 p38$^{C}$EBP$\beta$가 복합체 형성에 관여하는 것으로 나타났다. 이러한 결과들은 FRE-C/EBP isoform 복합체 형성이 IGF-I 유전자 발현의 조직 특이적 조절에 중요한 역할을 할 것으로 제안한다.할을 할 것으로 제안한다.

Molecular Cloning of Insulin-like Growth Factor-I (IGF-I) and IGF-II Genes of Marine Medaka (Oryzias dancena) and Their Expression in Response to Abrupt Transfer from Freshwater to Seawater

  • Kang, Yue-Jai;Kim, Ki-Hong
    • Fisheries and Aquatic Sciences
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    • 제13권3호
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    • pp.224-230
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    • 2010
  • Growth hormone (GH) is known as one of the main osmoregulators in euryhaline teleosts during seawater (SW) adaptation. Many of the physiological actions of GH are mediated through insulin-like growth factor-I (IGF-I), and the GH/IGF-I axis is associated with osmoregulation of fish during SW acclimation. However, little information is available on the response of fish IGF-II to hyperosmotic stress. Here we present the first cloned IGF-I and IGF-II cDNAs of marine medaka, Oryzias dancena, and an analysis of the molecular characteristics of the genes. The marine medaka IGF-I cDNA is 1,340 bp long with a 257-bp 5' untranslated region (UTR), a 528 bp 3' UTR, and a 555-bp open reading frame (ORF) encoding a propeptide of 184 amino acid (aa) residues. The full-length marine medaka IGF-II cDNA consists of a 639 bp ORF encoding 212 aa, a 109 bp 5' UTR, and a 416 bp 3' UTR. Homology comparison of the deduced aa sequences with other IGF-Is and IGF-IIs showed that these genes in marine medaka shared high structural homology with orthologs from other teleost as well as mammalian species, suggesting high conservation of IGFs throughout vertebrates. The IGF-I mRNA level increased following transfer of marine medaka from freshwater (FW) to SW, and the expression level was higher than that of the control group, which was maintained in FW. This significantly elevated IGF-I level was maintained throughout the experiment (14 days), suggesting that in marine medaka, IGF-I is deeply involved in the adaptation to abrupt salinity change. In contrast to IGF-I, the increased level of marine medaka IGF-II mRNA was only maintained for a short period, and quickly returned a level similar to that of the control group, suggesting that marine medaka IGF-II might be a gene that responds to acute stress or one that produces a supplemental protein to assist with the osmoregulatory function of IGF-I during an early phase of salinity change.

Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs

  • Song, Doo-Won;Ro, Woong-Bin;Sur, Jung-Hyang;Seung, Byung-Joon;Kang, Hyun-Min;Kim, Jong-Won;Park, See-Hyoung;Park, Hee-Myung
    • Journal of Veterinary Science
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    • 제22권6호
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    • pp.77.1-77.10
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    • 2021
  • Background: Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. Objectives: This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. Methods: The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5-175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5-79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2-57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6-70.5]) in healthy dogs. Conclusions: The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.

Influence of Refeeding of Protein, Carbohydrate and Fat on Hepatic Insulin-Like Growth Factor-I mRNA Level in Fasted Chicks

  • Kita, K.;Hangsanet, K.;Okumura, J.
    • Asian-Australasian Journal of Animal Sciences
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    • 제11권3호
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    • pp.245-248
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    • 1998
  • The influence of refeeding either protein, carbohydrate or fat on hepatic insulin-like growth factor-I (IGF-I) mRNA level in chicks which had been fasted for 2 days was examined. The hepatic IGF-I mRNA was measured by ribonuclease protection assay. Fasting reduced hepatic IGF-I mRNA levels to less than half of those in the fed control. When chicks were refed either a control, protein or carbohydrate diet, IGF-I mRNA levels significantly increased to those in the fed control until 2 hours of refeeding. Refeeding of fat did not alter hepatic IGF-I mRNA levels. The significant correlation between liver weight and hepatic IGF-I gene expression suggests that when chicks are refed after 2-d fasting, the acute increase in hepatic IGF-I gene expression brought about after refeeding may be partly regulated by the increase in liver protein metabolism.