• Title/Summary/Keyword: IGF-1 receptor

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The Regulation of Insulin-Like Growth (IGF) Factors and IGF Binding Proteins by High Glucose in Mesangial Cells

  • Park Soo-hyun
    • Biomedical Science Letters
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    • v.10 no.3
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    • pp.203-210
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    • 2004
  • It has been reported that glomerulosclerosis mediated by the dysfunction of mesangial cells and insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known the effect of high glucose on IGF-I, -II secretion, IGF-I receptor, and IGFBPs expression in the mesangial cells. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and oxidative stress in mesangial cells. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion and mRNA expression (P<0.05), which was blocked by PKC inhibitor (staurosporine, 10/sup -8/ M) and antioxidant (N-acetyl cystein, 10/sup -5/ M). High glucose decreased IGFBP-1 and -2 expression but increased IGFBP-5 expression. These alteration of IGFBPs by high glucose was also prevented by staurosporine and NAC, suggesting the role of PKC and oxidative stress. Indeed, high glucose increased PKC activity. Furthermore, high glucose-induced increase of lipid peroxide (LPO) formation was blocked by PKC inhibitors. In conclusion, high glucose alters IGF system via PKC-oxidative pathways in mesangial cells.

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Effects of Insulin and IGFS on Growth and Functional Differentiation in Primary Cultured Rabbit Kidney Proximal Tubule Cells -Growth and membrane transport-

  • Han, Ho-Jae;Park, Kwon-Moo
    • The Korean Journal of Physiology
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    • v.29 no.2
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    • pp.191-202
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    • 1995
  • The purpose of this study was to compare effects of insulin and IGFs on growth, apical membrane enzyme activities and membrane transport systems of primary cultured rabbit kidney proximal tubule cells. Results were as follows: 1. Insulin and IGF-I produced significant growth stimulatory effects at $5{\times}10^{-10}M.\;IGF-II(5×10^{-10}\;M)$ did not stimulate significant cell growth. 2. Insulin stimulated the phosphorylation of a 97 KD protein. It was difficult to determine whether this band represents insulin and/or the IGF-I receptor. 3. The activities of apical membrane enzymes (alkaline phosphatase, leucine aminopeptidase, and ${\gamma}-glutamyl \;transpeptidase)$ were observed to be diminished after the cells were placed in the culture environment. 4. The uptake of ${\alpha}-MG,$ Pi and Na was significantly increased in cells incubated with insulin or IGF-I, IGF-II had no effect on the uptake of these substrates. 5. Na-pump activity, as assayed by Rb uptake, was significantly increased in cells treated with insulin or IGFs. In conclusion, insulin and IGF-I exert stimulatory effects on growth and membrane transporter(glucose, Na, Pi, and Na-pump) activities in primary cultured rabbit kidney proximal tubule cells. IGF-II had no effect on cell growth and membrane transporter(glucose, Na and Pi) activities.

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

  • 남택정;권미진;류홍수;김경숙;변재형
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.28 no.3
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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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Modulation of the Somatotropic Axis in Periparturient Dairy Cows

  • Kim, Jin Wook
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.1
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    • pp.147-154
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    • 2014
  • This review focuses on modulation of growth hormone (GH) and its downstream actions on periparturient dairy cows undergoing physiological and metabolic adaptations. During the periparturient period, cows experience a negative energy balance implicating that the feed intake does not meet the total energy demand for the onset of lactation. To regulate this metabolic condition, key hormones of somatotropic axis such as GH, IGF-I and insulin must coordinate adaptations required for the preservation of metabolic homeostasis. The hepatic GHR1A transcript and GHR protein are reduced at parturition, but recovers on postpartum. However, plasma IGF-I concentration remains low even though hepatic abundance of the GHR and IGF-I mRNA return to pre-calving value. This might be caused by alternation in IGFBPs and ALS genes, which consequently affect the plasma IGF-I stability. Plasma insulin level declines in a parallel manner with the decrease in plasma IGF-I after parturition. Increased GH stimulates the lipolytic effects and hepatic glucose synthesis to meet the energy requirement for mammary lactose synthesis, suggesting that GH antagonizes insulin-dependent glucose uptake and attenuates insulin action to decrease gluconeogenesis.

Inhibition of mIGF-1 and mGHR Gene Expression using Tetracycline-Inducible RNAi System in Mouse Liver Cell (Tetracycline 유도적인 RNAi System을 이용한 생쥐 성장 관련 유전자의 발현 억제)

  • Son, Hye Jin;Koo, Bon Chul;Kwon, Mo Sun;Lee, Young Man;Kim, Teoan
    • Reproductive and Developmental Biology
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    • v.38 no.3
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    • pp.99-105
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    • 2014
  • In this study, to further understand the mechanism of animal growth and to develop a miniature transgenic animal model, we constructed and tested tetracycline-inducible RNAi system using shRNA targeting the mRNA of mouse insulin-like growth factor (mIGF-1) or mouse growth hormone receptor (mGHR) gene. Quantitative real-time PCR analysis of mouse liver cell (Hepa1c1c7) cells transfected with these vectors showed 85% or 90% of expression inhibition effect of IGF-1 or GHR, respectively. In ELISA analysis, the protein level of IGF-1 in the cells expressing the shRNA targeting IGF-1 mRNA was reduced to 26% of non-transformed control cells. Unexpectedly, in case of using shRNA targeting GHR, the IGF-1 protein level was decreased to 75% of control cells. Further experiments are needed to explain the lower interference effect of GHR shRNA in IGF-1 protein. Accumulated knowledge of this approach could be applicable to a variety of related biological area including gene function study, gene therapy, development of miniature animals, etc.

Antiapoptotic Effect of Aurintricarboxylic Acid; Extracellular Action versus Inhibition of Cytosolic Protein Tyrosine Phosphatases

  • Lee, Dong-Yoon;Kim, Mee-Kyung;Kim, Mi-Jeong;Bhattarai, Bharatraj;Kafle, Bhooshan;Lee, Keun-Hyeung;Kang, Jae-Seung;Cho, Hyeong-Jin
    • Bulletin of the Korean Chemical Society
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    • v.29 no.2
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    • pp.342-346
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    • 2008
  • Aurintricarboxylic acid (ATA) prevents apoptosis in a wide range of cell types, including PC12 cells. ATA is known to increase the phosphorylation level of IGF-1 receptor (IGF-1R) and downstream signaling proteins. ATA can translocate across the plasma membrane of PC12 cells and inhibit protein tyrosine phosphatases (PTPs) and, therefore, it is not clear whether ATA exerted its antiapoptotic effect through activation of IGF-1R or by inhibition of cytosolic PTPs. When PC12 cells, deprived of serum, were treated with Fab fragment of anti-IGF-1R antibody to prevent the binding of ATA to the extracellular domain of IGF-1R, ATA was found to penetrate into the cytosolic space of the cells. Under these conditions, the survival-promoting effects of ATA were abolished, and the increase of phosphorylation and characteristic cleavage of IGF-1R were not observed. These results indicate that the antiapoptotic effect of ATA in PC12 cells is due to the binding of ATA to the extracellular domain of IGF-1R and subsequent activation of the IGF-1R, not inhibition of cytosolic PTP(s).

Linseed oil supplementation affects fatty acid desaturase 2, peroxisome proliferator activated receptor gamma, and insulin-like growth factor 1 gene expression in turkeys (Meleagris gallopavo)

  • Szalai, Klaudia;Tempfli, Karoly;Zsedely, Eszter;Lakatos, Erika;Gaspardy, Andras;Papp, Agnes Bali
    • Animal Bioscience
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    • v.34 no.4
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    • pp.662-669
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    • 2021
  • Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated. Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (FADS2), peroxisome proliferator activated receptor gamma (PPARγ), and insulin-like growth factor 1 (IGF1) genes was analysed by means of quantitative reverse transcription polymerase chain reaction. Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic FADS2 levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The PPARγ expression was lower (p<0.05), whereas IGF1 was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in FADS2, PPARγ, and IGF1 gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control. Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased FADS2 expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased PPARγ expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased IGF1 expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group.

Chronic Effects of Nitrate Nitrogen on Juvenile Blackhead Seabream Acanthopagrus schlegelii in a Recirculating Aquaculture System (순환여과양식 시스템 내 감성돔(Acanthopagrus schlegelii) 치어에 미치는 질산성 질소의 만성적 영향)

  • Seo, Seok;Choi, Tae Gun;Park, Jeonghwan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.52 no.5
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    • pp.474-481
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    • 2019
  • This study evaluated the chronic effects of $NO_3-N$ on juvenile blackhead seabream Acanthopagrus schlegelii. The experiment used six identically configured recirculating aquaculture systems (435 L), with three tanks (70 L) each. The $NO_3-N$ concentrations studied were 0 (control), 62.5, 125, 250, 500, and 1,000 mg/L $NO_3-N/L$. Thirty juvenile blackhead seabream ($18.8{\pm}2.2g$) were stocked in each tank. Growth and hematological changes were evaluated after 120 days. At the end of the experiment, the growth, survival, and cortisol levels indicated that blackhead seabream were healthy in 500 mg $NO_3-N/L$. However, insulin-like growth factor I (IGF-1) and the IGF-1 receptor were significantly lower at 250, 500, and 1,000 mg $NO_3-N/L$ than in controls (62.5 and 125 mg $NO_3-N/L$). Juveniles were likely affected at a much lower $NO_3-N$ concentration than 250 mg/L $NO_3-N/L$ in terms of IGF-1 and the IGF-1 receptor. Therefore, for the sake of long-term fish welfare, the $NO_3-N$ should be maintained at lower than 250 mg/L for blackhead seabream in recirculating aquaculture systems.

Responses of Plasma IGF-1, IGFBPs and Hepatic GH Receptor to Growth Hormone Releasing Peptides (GHRP)-2 Administration and Energy Level in Wethers (거세면양에 있어서 에너지수준에 GHRP-2의 투여가 혈장 IGF-1, IGFBPs 및 hepatic GH 수용체에 미치는 반응)

  • Lee, Hong-Gu;Jin, Young-Cheng;Hidari, Hisashi;Choi, Yun-Jaie;Kim, Seon-Ku;Shin, Teak-Soon;Cho, Byung-Uuk;Kim, Yong-Gyun;Kim, Keun-Ki;Son, Hong-Joo;Lee, Sang-Mong;Park, Hyun-Chul;Kang, Han-Seok
    • Journal of Life Science
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    • v.18 no.7
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    • pp.931-939
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    • 2008
  • The purpose of this study was to determine the effect of energy supplement on responses of plasma insulin-like growth factor (IGF)-1 and IGF binding proteins (IGFBPs) to growth hormone-releasing peptide-2 (GHRP-2) administration in normal protein-fed wethers, and to observe the effect of GHRP-2 treatment on hepatic growth hormone (GH) receptor in well-fed wethers. Plasma IGF-1 and 39-42 kDa IGFBP-3 during the HENP (CP, crude protein 0.34 and TDN, total digestible nutrients 1.83 kg/day DM, dry matter intake) treatment period were higher than in the LENP (CP 0.32 kg and TDN 0.87 kg/day DM intake) period (P<0.05). The response of GH was stimulated by GHRP-2 ($12.5\;{\mu}g/kg$ body weight/day) administration during both of the feed treatment periods (P<0.05). The area under curve (AUC) increment and average concentration of GH (0-180 min) with GHRP-2 administration was higher during HENP treatment than LENP treatment (P<0.01). During the HENP treatment period from day 1 to day 7 of twice daily GHRP-2 treatment, the plasma IGF-1 increment was increased on days 2, 6 and 7 of GHRP-2 administration (P<0.05). On the basis of ligand blotting, the proportions of plasma 39-43 kDa IGFBP-3 during the HENP treatment period only showed a significant difference on days 6 and 7 with GHRP-2 administration. No significant difference in the specific binding of $^{125}I-labeled$ oGH to hepatic membranes was detected between the saline and GHRP-2 treatments of the HENP-fed wethers. These results suggest that the nutritional balance between energy and protein may affect the endogenous GH / IGF-1 axis as well as plasma IGFBP-3 levels.

Effects of high glucose concentration on IGF-I binding and glucose transporters in renal proximal tubule cells (신장 근위세뇨관세포에서 고포도당이 IGF-I 결합과 포도당운반계에 미치는 영향)

  • Han, Ho-jae;Park, Kwon-moo;Son, Chang-ho;Yoon, Yong-dal
    • Korean Journal of Veterinary Research
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    • v.37 no.2
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    • pp.301-310
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    • 1997
  • Diabetes mellitus is associated with a wide range of pathophysiological in the kidney. This study was designed to examine the effects of high glucose concentration on IGF-I binding and glucose transporters in renal proximal tubule cells. The results were as follows : The binding of $^{125}I-IGF-I$ reached the peak at the 30 minutes and gradually decreased by the time dependent manner. The binding of $^{125}I-IGF-I$ was inhibited by the unlabelled IGF-I($10^{-14}{\sim}10^{-8}M$) in a concentration dependent manner. The relative affinity of IGF-I receptor for IGF-I, IGF-II and insulin exhibited typical type 1 binding(IGF-I > insulin > IGF-II). However IGF-II did not compete for the cultured cell membrane $^{125}I-IGF-I$ binding site at $10^{-14}{\sim}10^{-8}M$. Under optimal conditions, IGF-I binding to the membranes from 5mM and 20mM glucose treated cells was analyzed. It was found that 20mM glucose treated cells exhibited higher binding activity for IGF-I. In order to further substantiate this increase in IGF-I binding sites, we performed affinity-labelling studies. The cross-linked cell membrane subjected to SDS-PAGE; labelled material was detected by autoradiography. 20mM glucose treated cells exhibited higher levels. The initial rate of $methyl-{\alpha}-D-glucopyranoside({\alpha}-MG)$ uptake was significantly lower($74.41{\pm}6.71%$) in monolayers treated with 20mM glucose than those of 5mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. IGF-I significantly increased ${\alpha}-MG$ uptake in both 5mM and 20mM glucose treated cells. However, 3-O-MG uptake was not affected by IGF-I in both conditions. In conclusion, 20mM glucose increased binding sites of $^{125}I-IGF-I$, inhibited Na/glucose cotransporter activity. But 20mM glucose did not change facilitated glucose transporter.

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