• Asian Pacific Journal of Cancer Prevention
• /
• 제17권12호
• /
• pp.5315-5320
• /
• 2016

Purpose: Tumor cell growth and sensitivity to chemotherapy depend on many factors, among which insulin-like growth factors (IGFs) may play important roles. The aim of the present study was to evaluate the levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in primary tumors and ascites as predictors of response to neoadjuvant chemotherapy in ovarian cancer (OC) patients. Materials and Methods: Tumor tissue samples and ascitic fluid were obtained from 59 patients with advanced OC. The levels of IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A were determined using ELISA kits. Taking into account the data on expression of these IGF-related proteins and outcome, logistic regression was performed to identify predictors of response to neoajuvant chemotherapy. Results: Human ovarian tumors expressed IGFs, IGFBP-3, IGFBP-4 and PAPP-A and these proteins were also present in ascites fluid and associated with its volume. IGFs and IGFBPs in ascites and soluble PAPP-A might play a key role in ovarian cancer progression. However, levels of proteins of the IGF system in tumors were not significant predictors of objective clinical response (oCR). Univariate analysis showed that the level of IGF-I in ascites was the only independent predictor for oCR. Conclusion: The level of IGF-I in ascites was shown to be an independent predictor of objective clinical response to chemotherapy for OC patients treated with neoadjuvant chemotherapy and debulking surgery.

• BMB Reports
• /
• 제32권3호
• /
• pp.266-272
• /
• 1999

The insulin-like growth factor (IGF) system consisting of IGF-I, IGF-II, IGF-receptors, and IGF-binding proteins (IGFBP) regulates the proliferation of a variety of cancer cell types. To examine whether a decrease in endogenous IGFBP-3 stimulates proliferation or inhibits differentiation, Caco-2 cells, a human colon adenocarcinoma cell line, were stably transfected with an anti-sense IGFBP-3 expression construct or pcDNA3 vector as control. Accumulation of IGFBP-3 mRNA and secretion of IGFBP-3 into serum-free conditioned medium, 9 days after plating, were significantly lower in Caco-2 cell clones transfected with anti-sense IGFBP-3 cDNA compared to the controls. The anti-sense clones grew at a similar rate to the controls for 8 days after plating, but achieved a higher final density between days 10 and 12. The levels of sucrase-isomaltase mRNA, a marker of enterocyte differentiation of Caco-2 cells, were lower in the anti-sense clones examined on day 9. In conclusion, proliferation of Caco-2 cells can be stimulated by lowering endogenously-produced IGFBP-3.

• Clinical and Experimental Reproductive Medicine
• /
• 제21권3호
• /
• pp.273-279
• /
• 1994

자궁내막이 생체내 insulin-like growth factor binding protein-1(IGFBP-1)의 혈중치를 유지하는데 얼마나 관여하는지를 평가해 보았다. Immunoreactive IGFBP-1의 혈중치의 측정을 위하여, 월경과다를 주소로 내원한 19명의 환자를 대상으로, gynecologic resectoscopy로 자궁내막 박리를 시행하였다. 자궁내막 박리를 시행한 환자의 혈중 IGFBP-1의 평균치는, 시행전과 비교할 때 감소된 소견을 보였으며, 월경주기와는 상관관계가 없었다. 이러한 소견으로 보아, 자궁내막이 혈중 IGFBP-1의 생성원의 하나로 사료되었다.

• Journal of Yeungnam Medical Science
• /
• 제12권2호
• /
• pp.319-330
• /
• 1995

임신시 발생하는 인슐린 저항성과 인슐린 분비 증가의 기전을 규명하기 위하여 Sprague-Dawley 종 암컷 흰쥐를 이용하여 정맥당부하 검사와 호르몬 및 지방 대사물질과 조직에서의 인슐린 수용체 결합, 당원질 합성효소를 분석한 결과를 요약하면 다음과 같다. 정맥당부하검사에서 임신군에서 전체적인 곡선이 대조군에 비하여 아래에 위치하였다. 그러나 당부하시 인슐린 분비는 현저히 증가하였으며 혈당에 대한 비(${\mu}U/mg$)로 비교하여 임신군에서 $56.9{\pm}8.9$였고 대조군에서 $23.6{\pm}2.8$로서 인슐린 저항성을 확인할 수 있었다. 인슐린 분비반응의 증가는 태반 호르몬인 progesterone의 증가와 강한 상관관계를 나타내었다. 당부하검사후 당원질 (mg/100mg tissue)은 골격근(soleus)에서는 임신군과 대조군간에 유의한 차이가 없었으나 간조직에서는 임신군에서 $4.7{\pm}0.9$으로 대조군의 $9.9{\pm}1.3$에 비하여 통계적으로 유의하게 감소하였다. 당원질로 합성된 $^{14}C$-glucose의 활동도도 마찬가지로 골격근에서는 임신군과 대조군간에 유의한 차이가 없었으나 간조직에서는 현저한 감소를 보였다. 당원질 합성 효소(glycogen synthase)는 골격근에서는 대조군이 높았고 간장조직에서는 임신군이 높았으나 유의한 차이는 없었다. 당부하검사후 간장조직의 crude membrane에서의 인슐린-인슐린 수용체 결합반응에서는 두 군 사이에 유의한 차이가 없었다. 이상의 결과로 보아 정상임신흰쥐에서 인슐린 저항성이 발생하였으나 인슐린 분비의 현저한 증가로 내당능의 감소는 나타나지 않았으며 인슐린의 분비증가는 progesterone의 증가와 상관관계가 있었다. 인슐린 저항성은 간에서 가장 현저하게 나타났으며 그 원인은 인슐린 수용체의 결합과정보다는 수용체 전 과정이거나 수용체 후 과정일 것으로 추정된다.

• Animal cells and systems
• /
• 제13권1호
• /
• pp.17-23
• /
• 2009

In previous studies, we found that Annexin I (Anx I) was co-secreted with insulin in response to glucose, and that extracellular Anx I stimulated the release of insulin via the Anx I binding site in rat pancreatic islets and the &-cell line. However, the role that Anx I plays in the insulin secretion was not established. Therefore, in this study, we evaluated the insulin secretion pattern in response to Anx I and the involvement of the cytoskeleton or PKC in Anx Istimulated insulin secretion in MIN6N8a cells. The peak time of insulin secretion in response to Anx I treatment corresponded with the second phase insulin secretion by glucose in the perifused pseudoislets. In addition, Anx I-stimulated insulin secretion was not affect by readily releasable pool depletion. Taken together, these findings indicate that Anx I treatment was associated with movement of the reserve pool of insulin. Furthermore, Anx I-stimulated insulin secretion was attenuated by treatment with a microfilament inhibitor, cytochalasin B, as well as by PKC down regulation. These results indicate that Anx I may be a regulator of second phase insulin secretion.

• Clinical and Experimental Pediatrics
• /
• 제59권5호
• /
• pp.231-238
• /
• 2016

Purpose: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. Methods: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. Results: The mean age of the participants was $12.9{\pm}0.3$ years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants ($7.8{\pm}1.9{\mu}g/mL$ vs. $6.0{\pm}1.6{\mu}g/mL$, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. Conclusion: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권9호
• /
• pp.3735-3740
• /
• 2015

Context: Insulin-like growth factor peptides play important roles in regulating cell growth, cell differentiation, and apoptosis, and have been demonstrated to promote the development of colorectal cancer (CRC). Objective: To examine the association of insulin-related biomarkers including insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and C-peptide with CRC risk and assess their relevance in predictive models. Materials and Methods: The odds ratios of colorectal cancer for serum levels of IGF-1, IGFBP-3 and C-peptide were estimated using unconditional logistic regression models in 100 colorectal cancer cases and 100 control subjects. Areas under the receiving curve (AUC) and integrated discrimination improvement (IDI) statistics were used to assess the discriminatory potential of the models. Results: Serum levels of IGF-1 and IGFBP-3 were negatively associated with colorectal cancer risk (OR=0.07, 95%CI: 0.03-0.16, P for trend <.01, OR=0.06, 95%CI: 0.03-0.15, P for trend <.01 respectively) and serum C-peptide was positively associated with risk of colorectal cancer (OR=4.38, 95%CI: 2.13-9.06, P for trend <.01). Compared to the risk model, prediction for the risk of colorectal cancer had substantially improved when all selected biomarkers IGF-1, IGFBP-3 and inverse value of C-peptide were simultaneously included inthe reference model [P for AUC improvement was 0.02 and the combined IDI reached 0.166% (95 % CI; 0.114-0.219)]. Conclusions: The results provide evidence for an association of insulin-related biomarkers with colorectal cancer risk and point to consideration as candidate predictor markers.

• 대한핵의학회지
• /
• 제17권2호
• /
• pp.35-40
• /
• 1983

To evaluated the usefulness of cultured human fibroblast for insulin receptor assay, the authors cultured fibroblast from biopsied normal adult female eyelid skin and assayed the insulin receptor with radioreceptor assay method. From the data obtained, percent of labeled insulin bound, numbers of insulin binding sites, affinity constants(Ka) and affinity of the empty sites(Ke) were calculated. The results were as follow; 1) The percent radioactivity bound of cultured fibroblast reached plateau at 4 hours $15^{\circ}C$ incubation. 2) The scatchard plot of insulin binding to cultured human fibroblast was curvilinear and the affinity to receptor was decreased with increased receptor occupancy. 3) The numbers of high affinity, low affinity and total insulin receptor of cultured fibroblasts were 852, 24,800 and 25,652 sites per cell. 4) High and low affinity constants of cultured fibroblasts were $3.4\times^{10}M^{-1},\;and\;1.08\times10^8M^{-1}$, and the affinity of empty site was $5.0\times10^8M^{-1}$.

• Molecules and Cells
• /
• 제20권2호
• /
• pp.280-287
• /
• 2005

The insulin-mediated Ras/mitogen-activated protein (MAP) kinase cascade was examined in SK-N-BE(2) and PC12 cells, which can and cannot produce reactive oxygen species (ROS), respectively. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) was much lower in SK-N-BE(2) cells than in PC12 cells when the cells were treated with insulin. The insulin-mediated interaction of IRS-1 with Grb2 was observed in PC12 but not in SK-N-BE(2) cells. Moreover, the activity of extracellular-signal-related kinase (ERK) was much lower in SK-N-BE(2) than in PC12 cells when the cells were treated with insulin. Application of exogenous $H_2O_2$ caused increased tyrosine phosphorylation and Grb2 binding to IRS-1 in SK-N-BE(2) cells, while exposure to an $H_2O_2$ scavenger (N-acetylcysteine) or to a phophatidylinositol-3 kinase inhibitor (wortmannin), and expression of a dominant negative Rac1, decreased the activation of ERK in insulin-stimulated PC12 cells. These results indicate that the transient increase of ROS is needed to activate ERK in insulin-mediated signaling and that an inability to generate ROS is the reason for the insulin insensitivity of SK-N-BE(2) cells.

• 한국식품영양과학회지
• /
• 제26권2호
• /
• pp.285-290
• /
• 1997

이상의 결과를 요약하연, 혈당값은 정상대조군 78{\pm}6.20mg/dl, 인슐린 비의존형 당뇨병 환자 $184{\pm}18.94mg/dl$로 인슐린 비의존형 당뇨병 환자의 혈당값이 유의적으로 높았다. IGF-I의 수준은 정상대조군 $9.32{\pm}1.48{\mu}g/ml$, 인슐린 비의존형 당뇨병 환자 $4.19{\pm}0.84{\mu}g/ml$로 인슐린 비의존형 당뇨병 환자의 IGF-I 수준이 유의적으로 낮았다. 인슐린 비의존형 당뇨병 환자의 혈청 중 IGFBP-1, -2는 증가한 반면, IGFBP-3, -4, -5는 감소하였다. IGFBP-3의 분해에 관여하는 효소는 PMSF, aprotinin, EDTA에 의해 저해되어 metal-dependent serine proteases임을 확인하였고, 효소의 크기가 대략 97,66kDa 이었으며 효소활성이 인슐린 비의존형 당뇨병 환자에게서 큼을 확인하였다.