• BMB Reports
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• 제52권6호
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• pp.385-390
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• 2019

Leptin, an adipokine regulating energy metabolism, appears to be associated with breast cancer progression. Insulin-like growth factor-1 (IGF-1) mediates the pathogenesis of breast cancer. The regulation of IGF-1 expression by leptin in breast cancer cells is unclear. Here, we found that leptin upregulates IGF-1 expression at the transcriptional level in breast cancer cells. Activating protein-1 (AP-1)-binding element within the proximal region of IGF-1 was necessary for leptin-induced IGF-1 promoter activation. Forced expression of AP-1 components, c-FOS or c-JUN, enhanced leptin-induced IGF-1 expression, while knockdown of c-FOS or c-JUN abrogated leptin responsiveness. All three MAPKs (ERK1/2, JNK1/2, and p38 MAPK) mediated leptin-induced IGF-1 expression. These results suggest that leptin contributes to breast cancer progression through the transcriptional upregulation of leptin via the MAPK pathway.

• BMB Reports
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• 제33권6호
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• pp.454-462
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• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.

• Asian-Australasian Journal of Animal Sciences
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• 제20권5호
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• pp.733-741
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• 2007

The effects of intra-duodenal infusion of methionine (Met), lysine (Lys) and leucine (Leu) on dry matter intake (DMI), the concentrations of insulin-like growth factor I (IGF-I), growth hormone (GH) and insulin in plasma, and liver IGF-I mRNA level were investigated in two experiments for Liuyang Black growing wether goats. In Experiment 1, three goats ($10.0{\pm}0.1$ kg) were fitted with ruminal, proximal duodenal and terminal ileal fistulaes to determine the infusion amounts of Met, Lys and Leu at the duodenum according to essential amino acid flows into the duodenum and their apparent digestibility. The infusion amounts were 0.77 g/d, 0.91 g/d and 0.58 g/d respectively. In Experiment 2, 4 groups of goats (($10.0{\pm}0.2$ kg) for each group, were cannulated at the duodenum, and were infused with a mixture of Met, Lys and Leu (Control), or mixtures with 21% Met, Lys or Leu replaced with glutamate respectively on a nitrogenous basis. The replacement of 21% Met, Lys or Leu with glutamate did not affect intakes of maize stover, concentrate or both (p>0.05) when compared with the control. The replacement of 21% Met or Lys significantly (p<0.05) reduced plasma GH, insulin and IGF-I concentrations and liver IGF-I mRNA level. The replacement of 21% Leu with glutamate reduced (p<0.05) plasma IGF-I concentration only, but not plasma insulin and GH, as well as liver IGF-I mRNA level (p>0.05). The close relationships between supplying Met and Lys in the lumen of the duodenum and plasma IGF-I, GH and insulin concentrations, as well as liver IGF-I mRNA level in this study indicate that the effects of the limiting amino acids on nutrition of animals are likely intermediated via their effects on these hormones, and these hormone profiles could be used as intermediate markers for the limiting order of amino acids.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1183-1186
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• 2012

Objective: To observe the effect of insulin-like growth factor-1 (IGF-1) on bone morphogenetic protein (BMP)-2 expression in hepatocellular carcinoma SMMC7721 cells. Methods: Cells were divided into blank control, IGF-1, IGF-1 + SB203580, and SB203580 groups. SB203580 was used to block the p38 MAPK signaling pathway. Changes in the expression of BMP-2, p38 MAPK, and phosphorylated p38, MERK, ERK and JNK were determined using reverse transcription polymerase chain reactions (RT-PCR) and Western blot analysis. Results: Protein expression of phosphorylated BMP-2, MERK, ERK, and JNK was significantly up-regulated by IGF-1 compared with the control group ($1.138{\pm}0.065$ vs. $0.606{\pm}0.013$, $0.292{\pm}0.005$ vs. $0.150{\pm}0.081$, $0.378{\pm}0.006$ vs. $0.606{\pm}0.013$, and $0.299{\pm}0.015$ vs. $0.196{\pm}0.017$, respectively; P<0.05). Levels of BMP-2 and phosphorylated MERK and JNK were significantly reduced after blocking of the p38MAPK signaling pathway ($0.494{\pm}0.052$ vs. $0.165{\pm}0.017$, $0.073{\pm}0.07$ vs. $0.150{\pm}0.081$, and $0.018{\pm}0.008$ vs. $0.196{\pm}0.017$, respectively; P<0.05), but such a significant difference was not observed for phosphorylated ERK protein expression ($0.173{\pm}0.07$ vs. $0.150{\pm}0.081$, P>0.05). Conclusion: IGF-1 can up-regulate BMP-2 expression, and p38 MAPK signaling pathway blockage can noticeably reduce the up-regulated expression. We can conclude that the up-regulatory effect of IGF-1 on BMP-2 expression is realized through the p38 MAPK signaling pathway.

• KSBB Journal
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• 제17권4호
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• pp.403-408
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• 2002

인체의 다양한 기능을 증진시키는 작용을 하는 것으로 알려진 IGF-I의 생체내 분비를 촉진시키기 위해 천연 생약재성분으로 구성된 YGF251을 개발하였고 YGF251의 효능을 측정하였다. 이중 맹검 시험 방식으로 40세에서 70세 사이의 성인 남녀 31명을 대상으로 IGF-I을 비롯하여 체중, 혈압, 간기능 검사 및 신장기능 검사를 실시하였다. YGF251 및 위약 투석 후의 IGF-I 함량변화에 대한 대응표본 검정결과는 YGF251 투여군에서 투여 전에는 245.6 ng/mL 이었는데 1개월 투여 후에는 269.3 ng/mL, 2개월 투여 후에는 275.6 ng/mL으로 유의하게 증가하였다 (p<0.05). 한편 위약 투여군에서는 투여 전에는 280.0 ng/mL이었으나 1개월 투여 후에는 239.2 ng/mL, 2개월 투여 후에는 230.2 ng/mL으로 유의하게 감소하는 결과를 보였다(p<0.05). 혈중 insulin함량은 실험군의 경우 YGF251 을 1개월 투여후 평균치로써 2배 정도의 증가를 보였으며 위약 투여군에서는 36% 정도 감소된 것으로 나타났다. 또한 YGF251투여에 의한 체중 및 혈압의 변화는 거의 나타나지 않았다. YGF251 투여에 의해 나타날수 있는 간기능 및 신장기능 변화를 관찰 하기 위해 여러 항목들의 수치는 측정 오차 범위내에서의 변화만을 나타내었다.

• Clinical and Experimental Pediatrics
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• 제48권11호
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• pp.1172-1178
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• 2005

목 적 : 소아 비만은 전세계적으로 증가하고 있는 추세이며, 신체적으로나 정신적으로 장애를 일으킨다. 특히 고혈압, 관상동맥질환, 당뇨병 등의 성인병이 문제가 되고 있다. 이에 비만 청소년에서 혈중 인슐린, 인슐린저항지수, 유리 지방산, IGF-I, IGFBP-3를 측정하였고, 심혈관 질환으로 진행할 수 있는 위험인자로 유용한지 알아보기 위해 본 연구를 실시하였다. 방 법 : 64명의 중등도 이상의 비만 청소년를 대상군으로 하였고, 같은 연령의 정상 청소년 20명을 대조군으로 하였다. 신장, 체중을 이용하여 비만도와 체질량지수를 산출하였고, 안정된 상태에서 수축기, 이완기 혈압을 측정하였다. 10시간 이상 금식 후 총 콜레스테롤, 중성지방, HDL 콜레스테롤, LDL 콜레스테롤, AST, ALT, 혈당, 인슐린, 유리지방산, IGF-I, IGFBP-3를 측정하였다. 결 과 : 인슐린은 비만군에서 $15.6{\pm}7.0{\mu}IU/mL$로 정상군보다 유의하게 높았고(P<0.01), 인슐린저항지수도 비만군에서 $64.6{\pm}31.6$으로 정상군보다 유의하게 높았다(P<0.01). IGF-I은 비만군에서 $498.1{\pm}122.2ng/mL$로 정상군보다 유의하게 높았고(P<0.05), IGFBP-3도 비만군에서 $3,777{\pm}4,721ng/mL$로 정상군보다 유의하게 높았다(P<0.05). 인슐린은 체질량지수(r=0.394), 비만도(r=0.304)와 양의 상관관계를 나타냈다. IGFBP-3는 비만도(r=0.419), 이완기 혈압(r=0.264), 체질량지수(r=0.247)와 양의 상관관계를 보였다. 인슐린저항지수는 체질량지수(r=0.595), 혈중 중성지방(r=0.515), 비만도(0.469)와 양의 상관관계를 나타냈다. 결 론 : 비만 청소년에서 혈중 인슐린, 인슐린저항지수, IGF-I, IGFBP-3가 증가하였다. 청소년 비만에서 이들 검사는 심혈관질환으로의 진행을 예측하는데 유용하리라 생각한다.

• 한국가축번식학회지
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• 제24권1호
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• pp.35-40
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• 2000

본 연구는 Wistar계 rat를 이용하여 포유기간 중 제한포유시기와 이유시기를 조절하여, 혈중 IGF- I 수준변화에 대해 검토하였다. NL군 (NL)은 포유자의 수를 8 마리로 조절하였으며, RL군 (RL)과 W군 (W)은 RL0, RL0, RL10, RLl5 및 RL20, 그리고 W0, W5, WI0, W15 및 W20으로 각각 5개 군으로 구분하여, RL군은 각 개시일에 포유자의 수를 8마리에서 4마리로 조절하였으며, W군은 각 개시일에 포유자의 수를 완전히 이유시켜 다음과 같은 결과를 얻었다. 1. NL군의 혈중 IGF-I 농도는 분만직후 (Day 0) 750.59$\pm$3.52ng/$m\ell$ 을 나타내어 15일까지 일정한 수준을 유지하다가 그 후 포유 25일에 1,690.20$\pm$4.42ng/$m\ell$ 까지 증가되었다. 2. 포유초기 RL군 (RL0, RL5)의 IGF- I 농도는 포유 10일에 RL0군과 RL5군에서 각각 1,395.90$\pm$3.45 및 1,351.73$\pm$3.23ng/$m\ell$로서 NL 군의 745.96$\pm$2.24ng/$m\ell$ 보다 유의적 (P＜0.05)으로 높게 나타났으나 포유 15일부터는 차이가 없었다. 3. 포유초기 W군의 IGF- I 농도는 이유 후 일주일 정도는 NL군에 비해 높은 수준 (P＜0.05)을 나타내다가 10일경에 NL군과 같은 수준으로 감소하였다. 포유자극의 강약은 난소의 생리적 변화와 함께 혈중 IGF- I의 농도를 조절하는 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5675-5680
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• 2013

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

• 한국발생생물학회지:발생과생식
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• 제20권3호
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• pp.179-185
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• 2016

The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

• 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.