• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10085-10089
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• 2015

Background: The insulin-like growth factor (IGF) system comprises a group of proteins that play key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. The aim of this study was to investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in hepatocellular carcinoma. Materials and Methods: Expression of IGF2, IGFBP3, and PTEN was analyzed by qRT-PCR. Lentivirus vectors were used to overexpress IGFBP3 in hepatocellular carcinoma cell (HCC) lines. The effect of IGFBP3 on proliferation was investigated by MTT and colony formation assays. Results: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells. Conclusions: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells.

• Asian-Australasian Journal of Animal Sciences
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• 제23권3호
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• pp.366-371
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• 2010

Twelve Suffolk${\times}$Small-tail-Han male sheep (body weight 21-26 kg), aged four months, were used to study the effects of volatile fatty acids (VFA) on IGF-I (insulin-like growth factor-I), IGFBP-3 (insulin-like growth factor binding protein-3), GH (growth hormone), insulin and glucagon in plasma, and IGF-I and IGFBP-3 in different tissues. The sheep were randomly divided into four groups with 3 sheep in each group. The sheep were sustained by total intragastric infusions and four levels of mixed VFA (the molar proportion of acetic acid, propionic acid and butyric acid was 65:25:10), which supplied 333, 378, 423 and 468 KJ energy/kg $W^{0.75}$/d, were infused into the rumen as experimental Treatments I, II, III and IV, respectively. The experiment lasted 12 days, of which the first 8 days were for pretreatment and the last 4 days for collection of samples. At the end of the experiment, blood samples were taken and then the sheep were slaughtered and tissue samples from the rumen ventral sac, rumen dorsal sac, liver, duodenum and Longissimus dorsi muscle were obtained. IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in different tissues were analysed. Results showed that the concentration of IGF-I, IGFBP-3, GH, insulin or glucagon in plasma and the content of IGF-I and IGFBP-3 in the rumen dorsal sac, rumen ventral sac, liver or Longissimus dorsi muscle were increased with VFA infusion level (p<0.05). No significant differences were found in duodenum IGF-I between Treatments I and II and in rumen dorsal sac IGFBP-3 between Treatments II and III (p>0.05). It was concluded that IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in rumen dorsal sac, rumen ventral sac, liver and Longissimus dorsi muscle were increased significantly with increasing level of ruminal infusion of mixed VFA.

• Fisheries and Aquatic Sciences
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• 제22권9호
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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.

• Asian-Australasian Journal of Animal Sciences
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• 제23권12호
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• pp.1668-1676
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• 2010

The somatotropic axis plays a key role in proliferation and differentiation of avian organs during both pre- and posthatching periods. This review discusses the complexity of regulation of the endocrine system for chicken development and growth by growth hormone (GH), insulin-like growth factor (IGF), and IGF binding protein (IGFBP). In addition, the thyrotropic axis, including thyrotropin-releasing hormone (TRH) and thyroid hormones ($T_4$ and $T_3$), is also involved in the GH-secreting pattern. In mammals, IGFI and -II are always sequestered in a 150 kDa non-covalent ternary complex. This complex consists of one molecule each of IGF-I or IGF-II, IGFBP-3 or IGFBP-5 and an acid labile subunit (ALS). Chick ALS is identified in different strains for the first time, and further investigation of the expression of ALS on developmental stage and ALS effect on IGF bioavailability may be addressed in the future.

• 대한수의학회지
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• 제40권3호
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• pp.489-496
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• 2000

본 연구에서는 Streptozotocin-induced 당뇨가 혈청과 간장 및 신장조직의 IGF-I, IGFBPs 및 IGF-I carrier protein 특성에 미치는 영향을 조사하였다. 혈액과 조직중의 IGF-I 농도는 방사면역측정법으로 측정하였고, IGFBPs 양상은 Western Ligand Blotting(WLB)으로 관찰하였으며, IGF-I carrier protein의 특성은 column chromatography로 측정하였다. 혈청과 IGF-I 농도는 당뇨군이 대조군에 비하여 유의하게 감소하였다 (p<0.01). 당뇨군은 대조군에 비하여 간장 IGF-I 농도는 유의하게 감소한 반면, 신장의 IGF-I 농도는 유의하게 증가하였다(p<0.01). 당뇨군은 대조군에 비하여 혈청과 간장의 IGFBP-3는 감소한 반면, IGFBP-2는 증가하였고, IGFBP-4는 변화가 없었다. 또한 당뇨군은 대조군에 비하여 150kDa carrier protein은 감소하였으며, 50kDa carrier protein은 증가하였다. 이상의 결과를 종합해볼 때 Streptozotocin-induced 당뇨는 혈청 뿐만 아니라 조직의 IGF-I/IGFBP system 변동에 영향을 미침을 알 수 있었다.

• Tuberculosis and Respiratory Diseases
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• 제58권2호
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• pp.120-128
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• 2005

연구배경 : 인슐린 양 성장 인자 결합 단백질-3 (IGF binding protein-3, IGFBP-3)는 생체내와 실험관내에서 인슐린 양 성장인자 매개 신호전달 체계를 억제하여 비소 세포성 폐암 세포의 증식을 조절하는 것으로 알려져 있다. 이에 본 연구에서는 비소세포성 폐암의 치료에 있어 IGFBP-3를 이용한 치료전략의 개발을 위하여 IGFBP-3(Ad5CMV-BP3)와 FTI SCH66336의 병용치료 상승작용을 분석하였다. 방 법 : 비소세포성 폐암 세포주의 성장에 Ad5CMV-BP3와 SCH66336의 병용투여가 미치는 효과를 측정하기 위하여 비소세포성 폐암 세포주와 IGFBP-3를 발현하는 recombinant adenovirus(Ad5CMV-BP3)를 이용하였고 흉선이 없는 nude mice의 등에 H1299 폐암 세포를 피하 주사한 후 Ad5CMV-BP3와 SCH66336의 병용치료 상승작용을 단일 치료와 비교 분석하였다. 결 과 : SCH66336과 Ad5CMV-BP3 병용처리는 단일 약제보다 더 큰 증식 억제효과 상승작용을 보였으며 nude mice에서도 병용치료 시 종양의 부피는 매우 의미 있는 감소를 보였다. 결 론 : 본 연구의 결과를 통하여 저자들은 SCH66336이 IGFBP-3와 병용투여시 실험실내와 생체내에서 비소 세포성 폐암세포의 세포자멸사에 상승적인 효과가 있다는 것을 처음으로 입증하였으며, 이는 비소세포성 폐암의 치료에 있어 Ad5CMV-BP3와 SCH66336의 병용치료가 임상적으로 사용될 수 있음을 시사하는 것이라 하겠다.

• Journal of Nutrition and Health
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• 제36권3호
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• pp.270-279
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• 2003

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid (LA) and exhibits anticarcinogenic activity in a variety of animal models. We have previously observed that CLA inhibited the growth of Caco-2 cells, a human colon adenocarcinoma cell line. The present study was performed to determine whether the growth inhibitory effect of CLA is related to change in secretion of IGF- II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate Caco-2 cell proliferation by an autocrine mechanism. Cells were incubated in serum-free medium with various concentrations of CLA or linoleic acid (LA). Immunoblot analysis of 24-hours, serum-free, conditioned medium using a monoclonal anti-IGF-IIantibody revealed that Caco-2 cells secreted both mature 6,500 Mr and higher Mr forms of pro IGF-II. The levels of pro IGF-II and mature IGF-IIwere decreased by 43 $\pm$ 2% and 53 $\pm$ 6%, respectively by treatment with 50 $\mu$ M CLA. LA slightly increased pro IGF- II levels. Results from Northern blot analysis showed that CLA decreased IGF-II mRNA levels at 50 $\mu$ M concentration suggesting that CLA regulation of IGF-II protein expression occurs partly at the transcriptional level. Ligand blot analysis of conditioned media using 1251-IGF-II revealed that CLA slightly decreased IGFBP-2 levels and increased IGFBP-4 levels. We confirmed our previous results that CLA inhibited cell growth in a dose-dependent manner but LA slightly increased cell growth. Exogenous IGF-II mitigated the growth inhibitory effect of CLA. These results indicate that the growth inhibitory effect of CLA may be at least in part mediated by decreasing IGF-II and IGFBP-2 secretion and increasing IGFBP-4 secretion in Caco-2 cells.

• Clinical and Experimental Pediatrics
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• 제51권7호
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• pp.722-728
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• 2008

목 적 : 건강한 만삭아의 제대혈에서 아디포넥틴, 렙틴, 인슐린, IGF-I, IGFBP-3를 측정하여 출생체중, 신장, 지방량과의 관계를 알아보고자 하였다. 또한 적정 체중아 그룹에서 이 호르몬들의 출생후 1개월 동안 변화에 대해서 살펴보기로 하였다. 방 법 : 임신과 관련된 합병증이 없었던 산모에서 태어난 200명의 건강한 만삭아(남아 109명, 여아 91명)를 대상으로 하여 제대혈을 채취하여 혈장과 혈청을 분리하였고 출생체중, 출생신장, 머리둘레, 가슴둘레, 피부두께를 측정하였으며 폰더랄지수를 계산하였다. 대상 신생아들을 출생체중에 따라 AGA (n=132), SGA (n=29), LGA (n=39)의 세 그룹으로 나누었다. 적정체중아 중 15명에서 생후 3일, 7일, 30일에 신생아의 혈액을 채취하여 제대혈과 같은 방법으로 분리하였고 체중과 신장을 측정하였다. 결 과 : 아디포넥틴과 인슐린, IGF-I은 AGA, LGA군보다 SGA군에서 더 낮았다. 렙틴은 AGA, SGA군보다 LGA군에서 더 높았다. 아디포넥틴과 렙틴, 인슐린, IGF-I, IGFBP-3는 출생체중과 피부두께의 합과 양의 상관관계에 있었다. 출생 시 신장과 양의 상관관계를 보인 호르몬은 아디포넥틴, 렙틴, IGF-I이었다. 아디포넥틴은 렙틴과 양의 상관관계를 보였으나 인슐린, IGF-I, IGFBP-3와는 상관관계가 없었다. IGF-I은 남아보다 여아에서 더 높은 수치를 보였다. 출생 후 1개월 동안 렙틴은 생후 7일까지는 생리적 체중감소와 더불어 감소하다가 그 후 증가하였고 IGF-I 또한 생후 3일에 감소하다가 1개월 후 급격한 증가를 보였다. 결 론 : 아디포넥틴과 렙틴, 인슐린, IGF-I, IGFBP-3 모두 태아의 성장에 중요한 역할을 하며, 아디포넥틴은 인슐린, IGF-I 축과는 다른 기전으로 태아의 성장을 조절한다고 생각할 수 있었다. IGF-I은 남아에서보다 여아에서 더 높은 수치를 보여서 IGF-I의 성별간의 차이가 자궁 내에서도 존재하였다. 생후 1개월 동안의 성장에 다른 호르몬보다 IGF-I 이 더 중요한 역할을 한다는 사실을 알 수 있었다.

• 대한의생명과학회지
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• 제10권3호
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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.

• Fisheries and Aquatic Sciences
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• 제23권2호
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• pp.3.1-3.8
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• 2020

Background: The IGF system plays important roles in controlling growth, development, reproduction, and aging of organisms. Methods: To estimate maturation of the Pacific oyster Crassostrea gigas, we investigated the expression of insulin-like growth factor (IGF) system components and sex-specific genes. To determine the role of the IGF system in the growth and spawning period of female and male oysters, we examined mRNA expression levels of the C. gigas insulin receptor-related receptor (CIR), IGF binding protein complex acid labile subunit (IGFBP_ALS), and molluscan insulin-related peptide (MIP), as well as those of vitellogenin (Vg) and receptor-type guanylate cyclase (Gyc76C) in gonads of C. gigas collected between April and October, when sex can be determined visually in this species. Results: We found that MIP, IGFBP_ALS, and CIR mRNA expression levels were dependent on sex and month and were greater in males than in females. CIR and Vg mRNA expression levels were very similar among females, whereas IGF system components and Gyc76C were very similarly expressed among males. The highest expression values were observed in May, when oysters are mature; CIR and Vg mRNA expression levels were highest in females, and those of MIP, IGFBP_ALS, CIR, and Gyc76C were highest in males. Interestingly, we observed a 1:1 proportion of females to males during this period. Conclusion: Our results suggest that IGF system components, as well as Vg and Gyc76C, are associated with sexual maturation in C. gigas.