• Title/Summary/Keyword: insulin/IGF-1

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Bovine Growth Hormone and Milk Fat Synthesis: from the Body to the Molecule - Review -

  • Kim, W.Y.;Ha, J.K.;Han, In K.;Baldwin, R.L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.10 no.4
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    • pp.335-356
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    • 1997
  • Injection of bovine growth hormone (bGH) to lactating dairy cows increases milk yield and yields of milk components including fat. It is generally believed that most of the anabolic effects derived from bGH in animal tissues are primarily mediated by IGF-1. IGF-1 is a strong anabolic peptide in the plasma of animals and exerts mitogenic and metabolic effects on target cells. Contrary to most protein hormones, the majority of IGF-1 in circulation is bound to the binding proteins (IGFBPs) which are known to be responsible for modifying the biological actions of IGF-1, thus making determinations of IGF-1 actions more difficult. On the other hand, fat is a major milk component and the greatest energy source in milk. Currently, the fat content of milk is one of the major criteria used in determining milk prices. It has been known that flavor and texture of dairy products are mainly affected by milk fat and its composition. Acetyl-CoA carboxylase (ACC) is the rate limiting enzyme which catalyzes the conversion of acetyl-CoA to malonyl-CoA for fatty acid synthesis in 1ipogenic tissues of animals including bovine lactating mammary glands. In addition to the short-tenn hormonal regulation of ACC by changes in the catalytic efficiency per enzyme molecule brought about by phosphorylation and dephosphorylation of the enzyme, the long-term hormonal regulation of ACC by changes in the number of enzyme molecules plays an essential role in control of ACC and lipogenesis. Insulin, at supraphysiological concentrations, binds to IGF-1 receptors, thereby mimicking the biological effects of IGF-1. The receptors for insulin and IGF-1 share structural and functional homology. Furthermore, epidermal growth factor increased ACC activity in rat hepatocytes and adipocytes. Therefore, it can be assumed that IGF-1 mediating bGH action may increase milk fat production by stimulation ACC with phosphorylation (short term) and/or increasing amounts of the enzyme proteins (long term). Consequently, the main purpose of this paper is to give the readers not only the galactopoietic effects of bGH, but also the insight of bGH action with regard to stimulating milk fat synthesis from the whole body to the molecular levels.

Effects of Glucose and IGF-I on Expression of Glucose Transporter 1 (Glut1) and Development of Preimplantation Mouse Embryo (생쥐의 착상전 배아의 발생과 Glucose Transporter 1 (Glut1) 발현에 대한 포도당과 IGF-I의 영향)

  • 전한식;계명찬;김종월;강춘빈;김문규
    • Development and Reproduction
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    • v.2 no.2
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    • pp.205-212
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    • 1998
  • A sodium-independent facilitative glucose transporter 1 (Glut1) is a major route by which glucose can be transported across the plasma membrane of mouse embryo. Although it has been known that insulin-like growth factor-I (IGF-I) promotes glucose transport into the mouse embryo, whether IGF-I directly regulates transcription of Glut1 has been uncovered in mouse preimplantation embryo. This study was aimed to elucidate the role of glucose and IGF-I in development and Glut1 expression in preimplantation mouse embryo. Two-cell embryos developed in blastocyst regardless of the glucose in the presence of pyruvate. IGF-I significantly increased the number of blastomeres in the mid-blastula. Deprivation of glucose did not affect the amount of Glut1 transcripts in morula cultured from 2-cell embryo. IGF-I potentiated Glut1 expression in morula cultured from 2-cell embryo even in the absence of glucose. Taken together, it is concluded that depletion of glucose does not promote Glut1 expression the in morula cultured form 2-cell embryo, and that increment of Glut1 expression possibly mediates embryotropic effect of IGF-I on preimplantation mouse embryo.

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Insulin-Like Growth Factor-I Induces Androgen Receptor Coactivator Expression in Skeletal Muscle Cells through the p38 MAPK and ERK1/2 Pathways (C2C12 세포에서 insulin-like growth factor-I이 p38 MAPK, ERK1/2 신호전달 경로를 통해 엔드로젠 수용체 coactivator 발현에 미치는 영향)

  • Park, Chan-Ho;Kim, Hye-Jin;Kim, Tae-Un;Lee, Won-Jun
    • Journal of Life Science
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    • v.21 no.2
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    • pp.242-250
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    • 2011
  • Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) coactivators are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR coactivators and IGF-I in skeletal muscle cells has not been previously examined. In this study, the effects of IGF-I treatment on the gene expression of AR coactivators in the absence of AR ligands and the roles of the p38 MAPK and ERK1/2 signaling pathways in IGF-I-induced AR coactivators induction were examined. C2C12 cells were treated with 250 ng/ml of IGF-I in the presence or absence of specific inhibitors p38 MAPK (SB203580) or ERK1/2 (PD98059). Treatment of C2C12 cells with IGF-I resulted in increased in GRIP-1, SRC-1, and ARA70 protein expression. The levels of GRIP-1, SRC-1, and ARA70 mRNA were also significantly increased after 5min of IGF-I treatment. IGF-I-induced AR coactivator proteins were significantly blocked by pharmacological inhibitors of p38 MAPK and ERK1/2 pathways. However, there was no significant effect of those inhibitors on IGF-I-induced mRNA level of AR coactivators, suggesting that AR coactivators are post-transcriptionally regulated by IGF-I. Furthermore, the present results suggest that IGF-I stimulates the expression of AR coactivators by cooperative activation of the p38 MAPK and ERK1/2 pathways in C2C12 mouse skeletal muscle cells.

Effect of KiFAY on Performance, Insulin-like Growth Factor-1, and Thyroid Hormones in Broilers

  • Kini, Amit;Fernandes, Custan;Suryawanshi, Dayaram
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.10
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    • pp.1451-1457
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    • 2016
  • A comparative study was performed to investigate the efficacy of KiFAY as a feed additive on performance parameters, thyroid, and pancreatic hormone levels in broilers. Ninety birds (Vencobb 400) were randomly divided into three groups viz., Control (no DL-methionine supplementation), Treatment1 (containing added DL-methionine) and Treatment 2 (containing KiFAY and without DL-methionine supplementation). The performance parameters (weekly body weight, body weight gain, feed intake, and feed consumption ratio) were recorded and calculated during the whole study of 4 weeks. Analyses of insulin and insulin-like growth factor (IGF 1), triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) were performed at the end of the study. The results show that birds on supplementation of KiFAY performed significantly (p<0.001) better than other treatments. The weekly body weight, body weight gain, feed in-take and feed consumption ratio improved in KiFAY treated birds. The study found an increase in insulin and IGF1 levels (p<0.001) in KiFAY compared with the other treatments. Serum T3, T4, and TSH levels in the Treatment 2 were higher than other treatments (p<0.001). The KiFAY supplementation was able to improve performance with associated responses at a hormonal level in broilers.

Regulation of adductor muscle growth by the IGF-1/AKT pathway in the triploid Pacific oyster, Crassostrea gigas

  • Kim, Eun-Young;Choi, Youn Hee
    • Fisheries and Aquatic Sciences
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    • v.22 no.9
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    • pp.19.1-19.10
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    • 2019
  • We investigated the insulin-like growth factor 1 (IGF-1)/AKT signaling pathway involved in muscle formation, growth, and movement in the adductor muscle of triploid Pacific oyster, Crassostrea gigas. Large and small triploid oysters (LTs and STs) cultured under identical conditions were screened, and the signaling pathways of individuals with superior growth were compared and analyzed. mRNA and protein expression levels of actin, troponin, tropomyosin, and myosin, proteins important in muscle formation, were higher in LTs compared with STs. Expression levels of IGF-1, IGF binding protein (IGFBP), and IGFBP complex acid-labile subunit were also higher in LTs compared with STs. Phosphorylation of the IGF receptor as well as that of AKT was high in LTs. In addition, the expression of phosphomammalian target of rapamycin and phospho-glycogen synthase kinase $3{\beta}$ was increased and the expression of Forkhead box O3 was decreased in LTs. Therefore, we suggested that the IGF-1/AKT signaling pathway affects the formation, growth, and movement of the adductor muscle in triploid oysters.

Oral Insulin-like Growth Factor-I Combined Alters Intestinal Protein Synthesis in Parenterally-fed Piglets

  • Park, Yoo-Kyoung;Sharon M. Donovan
    • Nutritional Sciences
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    • v.3 no.2
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    • pp.57-65
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    • 2000
  • Partial enteral nutrition (PEN) supplemented with insulin-like growth factor-I (IGF-I) to neonatal piglets receiving parenteral nutrition increases lactase-phlorizin hydrolase (LPH) activity, but not LPH mRNA. The goal of the current study was to investigate the mechanism by which IGF-I up-regulates LPH activity. We hypothesized that IGF-I regulates LPH synthesis post-transcriptionally. Methods: Newborn piglets (n=15) received 100% parenteral nutrition (TPN), 80% parenteral nutrition + 20% PEN (PEN), or PEN + IGF-I (1.0mg/kg/d). On day 7, two stable isotopes of leucine, [$^2 H_3$]-leucine and [$^{13}C_1$]-L-leucine were intravenously administered to measure mucosal protein and brush LPH (BB LPH) synthesis. Results: Weight gain, nutrient intake and jejunal weight and length were similar among the treatment groups. PEN increased mucosal weight, villus width and cross-sectional area, LPH activity, mRNA expression and the abundance of proLPHh compared to 100% TPN (p<0.05). IGF-I further increased mucosal weight, LPH activity and LPH activity per unit BB LPH ~2-fold over PEN alone (p<0.05), but did not affect LPH mRNA or the abundance of proLPHh or mature LPH. Isotopic enrichment of [$^2 H_3$]-leucine and [$^{13}C_1$]-L-leucine in plasma, mucosal protein and LPH precursors, and the fractional and absolute synthesis rates of mucosal protein and LPH were similar among the treatment groups. Total mucosal protein synthesis was increased 60% (p<0.05) and LPH synthesis tended (p=0.14) to be greater in the IGF-I treated animals compared to the other two groups. Conclusions: The primary mechanism by which IGF-I up-regulates LPH may be post-translational, either via reducing LPH turnover, or by specifically altering LPH activity.

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Association of growth hormone and insulin-like growth factor I genotype with body weight, dominance of body weight, and mRNA expression in Korat slow-growing chickens

  • Sinpru, Panpradub;Bunnom, Rujjira;Poompramun, Chotima;Kaewsatuan, Pramin;Sornsan, Sirangkun;Kubota, Satoshi;Molee, Wittawat;Molee, Amonrat
    • Animal Bioscience
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    • v.34 no.12
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    • pp.1886-1894
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    • 2021
  • Objective: Growth hormone (GH) and insulin-like growth factor I (IGF-I) play a critical role in animal growth rates. We aimed to investigate the effect of GH and IGF-I genotypes on body weight (BW), dominance, and gene expression in slow-growing chickens at different ages. Methods: A total of 613 Korat chickens (KRs) were bred and divided into three groups by genotype - A1A1, A1A3, and A3A3 for GH and AA, AC, and CC for IGF-I. Chickens were weighed every two weeks, and liver and breast muscle tissues were collected at 10 weeks of age. Genetic parameters of KRs were estimated using ASReml software. The GH and IGF-I mRNA levels were measured by quantitative polymerase chain reaction. Significant differences between traits were analyzed using the generalized linear model. Results: A significant effect of GH genotypes on BW was found at most ages, and the A1A1 genotype had the highest value of BW. Compared with the A3A3 genotype, the A1A1 and A1A3 genotypes showed a higher dominance effect at 0 and 2 weeks, and genotype A1A1 had the highest value of dominance at 8 weeks of age. A difference in GH mRNA levels between genotypes was detected in breast muscle at 6 weeks and in the liver tissue at 2 weeks. In the case of IGF-I gene, the AA genotype had the highest BW at the beginning of life. Significant differences in BW dominance were found at 2 weeks. However, IGF-I mRNA levels were not different among genotypes in both breast muscles and liver tissues. Conclusion: Our results revealed that GH and IGF-I influence growth, but may not be involved in heterosis. GH can be used as a marker gene in selection programs for growth because the homozygous genotype (A1A1) had the highest BW at all ages. The IGF-I is not a useful marker gene for selection programs.

Longevity regulation by NMD-mediated mRNA quality control

  • Son, Heehwa G.;Lee, Seung-Jae V.
    • BMB Reports
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    • v.50 no.4
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    • pp.160-161
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    • 2017
  • Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remains largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activity of NMD decreases during aging, raising the possibility that RNA quality declines in old animals. We then show that key components of NMD complex are required for prolonged lifespan in C. elegans. In addition, animals with reduced insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS), a representative longevity model, display increased NMD activity. Thus, up-regulation of NMD appears to play crucial roles in longevity conferred by reduced IIS via enhancing mRNA quality control. As both IIS and NMD pathways are evolutionarily conserved, mammals including humans may be equipped with similar RNA quality control systems to achieve longevity.

The Protective Effect of Ginseng Saponin against High Glucose-Induced Secretion of Insulin-Like Growth Factor (IGF)-I in Primary Cultured Rabbit Proximal Tubule Cells (신장 근위세뇨관 세포에서 고포도당에 의한 IGF-I 분비 촉진작용에 있어서 인삼의 차단효과)

  • Jung, Ho-Kyoung;Lim, Suel-Ki;Park, Min-Jung;Bae, Chun-Sik;Yoon, Kyung-Chul;Han, Ho-Jae;Park, Soo-Hyun
    • Journal of Ginseng Research
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    • v.33 no.1
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    • pp.26-32
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    • 2009
  • Diabetic nephropathy is associated with the dysfunction of proximal tubule cells. Insulin-like growth factor 1(IGF-I) has also been considered to play an important role in the development of diabetic nephropathy. Ginsenosides have been used as a remedy for diabetes in Asian countries. Therefore, we examined the preventive effect of ginsenosides against high glucose-induced alteration of IGF-I secretion in the primary cultured proximal tubule cells. In present study, Ginseng saponin (GS) completely blocked high glucose-induced stimulation of IGF-I secretion in proximal tubule cells, whereas panaxatriol (PI) and panaxadiol (PD) partially suppressed. In addition, high glucose stimulated cAMP formation and protein kinase C(PKC) activity from cytosolic to membrane fraction. GS completely prevented high glucose-induced stimulation of cAMP and PKC activity while PT and PD partially did. Furthermore, high glucose-induced stimulation of IGF-I was blocked by the treatment of PKI (protein kinase A inhibitor) and bisindolylmaleimide I (protein kinase C inhibitor). In conclusion, GS prevented high glucose-induced dysfunction of proximal tubule cells.

Loss of Imprinting of Insulin-Like Growth Factor 2 is Associated with Increased Risk of Primary Lung Cancer in the Central China Region

  • Zhang, Ming;Wu, Cui-Huan;Zhu, Xiao-Ling;Wang, You-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7799-7803
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    • 2014
  • Background: To determine the imprinting status of the IGF2 in Chinese patients with primary lung cancer and to analyze the clinical significance of the loss of imprinting (LOI) of IGF2. Materials and Methods: PCRRFLP and RT-PCR-RFLP were carried out to select heterozygous cases for the ApaI polymorphism within exon 9 of the IGF2 gene and further analyze IGF2 LOI in 64 lung cancer patients, respectively. Results: Of 64 lung cancer patients, 31 were heterozygous for IGF2. The positive rates of IGF2 LOI of lung cancer foci, matched paracancer tissues, and normal lung tissues were 77.4% (24/31), 61.3% (19/31), and 29.0% (9/31), respectively. The LOI differences for IGF2 among the three groups were statistically significant (${\chi}^2=15.267$, p=0.000), and the LOI frequency of IGF2 in normal lung tissue was significantly lower than that in lung cancer foci and paracancer tissues (${\chi}^2=14.577$, p=0.000; ${\chi}^2=6.513$, p=0.011). No statistical difference was observed between the lung tumor group and the matched paracancer group (${\chi}^2=1.897$, p=0.168). The prevalence of advanced clinical stages (${\chi}^2=2.379$; p=0.017) and lymph node metastasis (${\chi}^2=5.552$; p=0.018) was significantly higher for LOI-positive paracancer tissues than for LOI-negative paracancer tissues. Conclusions: IGF2 LOI is highly frequent in Chinese primary lung cancer patients, especially those with increased risk of lymph node metastasis and advanced clinical stages. IGF2 LOI may be an early epigenetic event in human lung carcinogenesis.