• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제33권6호
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• pp.617-624
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• 2007

Insulin-like growth factor(IGF) is the most abundant growth factor in bone matrix. Recent studies have shown that it can sensitize apoptotic cell death of osteoblasts. Thus, this study investigated whether IGF-II aggravates irradiation-induced cell death of osteoblasts. Cultured MC3T3 osteoblasts were irradiated and IGF-II was added at the concentration of 50 ng/ml immediately after the irradiation. Cell viability was measured by MTT assay. Changes in cell death and cell cycle were analyzed by flow cytometry. The expression of proapoptotic gene bax and antiapoptotic gene bcl-2 was quantified by real time RT-PCR and Western blot. A dose of 30 Gy caused G2/M arrest and increased cell death through both necrosis and apoptosis, while irradiation from 4 to 10 Gy little affected cell cycle and death. IGF-II treatment reduced cell viability without stimulating cell proliferation and changing cell cycle. Combined treatment of IGF-II with irradiation decreased cell viability and proliferation and increased cell death along with G2/M arrest. These effects were not different from those of irradiation only. At transcriptional and protein levels, IGF-II treatment did not affect bax and bcl-2 expression, whereas irradiation increased the expression ofbax without changes in bcl-2. IGF-II in combination with irradiation showed similar findings. These results suggest that IGF-II could modulate apoptotic cell death through mechanisms other than an imbalance between bax and bcl-2 gene expression, although its effect was overridden by irradiation.

• 대한수의학회지
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• 제43권4호
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• pp.563-571
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• 2003

Dysfunction of mesangial cells has been contributed to the onset of diabetic nephropathy. Insulin like growth factors (IGFs) are also implicated in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion in the mesangial cells. Furthermore, the relationship between cAMP and high glucose on the secretion of IGFs was not elucidated. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. Glucose increased IGF-I secretion in a time- (>8 hr) and dose- (>15 mM) dependent manner (p<0.05). Stimulatory effect of high glucose on IGF-I secretion is predominantly observed in 25 mM glucose (high glucose), while 25 mM glucose did not affect cell viability and lactate dehydrogenase release. High glucose also increased IGF-II secretion. The increase of IGF-I and IGF-II secretion is not mediated by osmotic effect, since mannitol and L-glucose did not affect IGF-I and IGF-II secretion. 8-Br-cAMP mimicked high glucose-induced secretion of IGF-I and IGF-II. High glucose-induced stimulation of IGF-I and IGF-II secretion was blocked not by pertussis toxin but by SQ 22536 (adenylate cyclase inhibitor). Rp-cAMP (cAMP antagonist), and myristoylated protein kinase A (PKA) inhibitor amide 14-22 (protein kinase A inhibitor). These results suggest that cAMP/PKA pathways independent of Gi protein may mediate high glucose-induced increase of IGF-I and IGF-II secretion in mesangial cells. Indeed, glucose (>15 mM glucose) increased cAMP formation. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via cAMP/PKA pathway in mesangial cells.

• 한국가정과학회지
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• 제9권1호
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• pp.81-88
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• 2006

IGFs and IGFBPs have an important role in controlling glucose homeostasis. This study was conducted to investigate the changes of insulin-like growth factor(IGF)-I. IGF-II and IGF binding proteins (IGFBPs) on fasting and postprandial state in Korean diabetes, Twenty eight healthy subjects and fifty seven diabetic patients participated in this study. The healthy subjects were not knowingly suffered from any disease and were not receiving any medical treatment, and diabetic subjects were undergo medical treatment, continuously. Weight and height were measured and body mass index (BMI) was calculated as weight (kg) divided by the square of height (m2). Blood pressure was measured. Plasma lipid profiles were analyzed by enzymatic methods, plasma Insulin and glucose levels were measured in fasting and postprandial state, respectively. The levels of serum IGFs and IGFBP-3 were measured by radioimmunoassay (RIA). The levels of glucose and insulin were significantly higher in diabetes than normal subjects on fasting as well as postprandial state (p<0.0l). The levels of IGF-I was significantly lower in diabetes than normal subjects, however in postprandial state, there was no significant difference between diabetes and control subjects, The levels of IGF-II were significantly lower in diabetes than control subjects both fasting and postpradial state, The level of IGFBP-3 were not significantly different between diabetes and normal subjects. Fasting IGF-I, IGF-II and IGFBP-3 levels were positively correlated with those levels on postprandial state, fasting IGe levels of IGF-I levels were positively correlated with fasting insulin levels, and postprandial IGF-I levels were positively correlated with fasting glucose, postprandial insulin and postprandial insulin levels, plasma triglyceride levels were correlated with plasma triglyceride levels. The IGFBP-3 levels were not correlated with IGF components, glucose, insulin and plasma lipids, These results demonstrate that in diabetes, the components IGF-I/IGFBPs system were significantly correlated with plsma glucose and insulin levels both fasting and postprandial state.

• Journal of Veterinary Science
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• 제22권6호
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• pp.77.1-77.10
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• 2021

Background: Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. Objectives: This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. Methods: The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5-175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5-79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2-57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6-70.5]) in healthy dogs. Conclusions: The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.

• 대한예방한의학회지
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• 제10권2호
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• pp.51-62
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• 2006

Psoriasis is a chronic skin disease characterized by angiogenesis. It has been reported that growth factor as vascular endothelial growth factor(VEGF) and insulin like growth factor(IGF) II are overexpressed in psoriatic epidermis. To investigate the inhibitory effects of IGF-II induced VEGF and HIF-1${\alpha}$ expression by RR extracts, we performed MTS assay, western blots using HaCaT cells. RR extracts significantly reduced IGF-II induced HIF 1${\alpha}$ protein level via MAPK pathway in HaCaT cells. Also, RR extracts inhibited IGF-II induced VEGF mRNA and protein expression levels in the HaCaT keratinocytes. These results suggest that inhibition of HIF-1${\alpha}$ and VEGF expressions by RR extracts contributes to the anti angiogenic effects.

• 한국임상수의학회지
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• 제20권3호
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• pp.263-273
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• 2003

본 연구는 흰쥐의 난소제거로 유발한 골다공증에 대한 흥화씨(Carhamus inctorius L)의 투여 효과를 알아보기 위하여 혈청내 호르몬과 골소주의 변화를 관찰하였다 실험동물은 4개월 령의 흰쥐를 난소절제를 실시하여 골다공증을 유발 시킨 후 실험에 이용하였으며 30일간 격일 간격으로 0.03g/kg의 용량을 투여 하였다. 혈청 내에서 Insulin-like Growth Factors, Insulin-like Growth Factor binding protein-3 (IGFBP-3), Estrogen, Bone-specific alkaline phosphotase, Calcium, and Phospotase를 매 10일 간격으로 측정하였으며 비골의 골간을 채취하여 조직 형태학적인 검사를 실시하였고 체중에 대한 대퇴골 무게를 측정하였다. 홍화씨 투여 10일과 20일에서는 혈청내 IGF-I, IGF-II그리고 IGFBP-3의 변화는 대조군에 비하여 유의성 있는 변화를 관찰할 수 없었으나 홍화씨 투여 30일에 있어서는 IGF-I, IGF-II그리고 IGFBP-3의 변화가 대조군에 비하여 현저히 높은 유의서 있는 변화를 관찰할 수 있었다(p<0.05). Bone alkaline phosphatase(BALP)에 있어서도 홍화씨 투여 30일 에 가장 많은 변화가 있었으나 estrogen과 체중에 대한 대퇴골의 무게에 있어서는 유의성 있는 변화를 관찰하지 못했다. 오히려 이시기에 난소를 절제하지 않는 대조군의 estrogen치가 높게 나타났다. 난소절제로 골다공증을 유발시킨 흰쥐에 있어서 흥화씨의 투여는 혈청내 IGFs, IGFBP-3 and BALP을 높임으로서 골다공증 치료에 효과가 있는 것으로 사료됩니다.

• 한국식품영양과학회지
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• 제29권3호
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• pp.493-499
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• 2000

골감소증 환자의 혈청중에 존재하는 IGFBP-5의 존재와 변화를 검토한 결과, 골감소즈 환자에서는 정상 대조군에 비해 IGFBP-5가 감소하였는데 이 변화는 IGFBP-5의 분해효소가 작용하기 때문인 것으로 나타났다. IGFBP-5에 작용하는 단백질분해효소 저해제중 metallo계인 EDTA 및 1,10-phenanthroline과 seriner계인 aprotinin, heparin, heparin cofactor 2(HC2), heparine+HC2가 IGFBP-5에 대해 저해효과가 크므로 metalloprotease이면서 serine protease의 성질을 가지는 효소들이 IGFBP-5에 작용하였다. IGF-I과 IGF-II 그리고 insulin은 효소 활성에 아무런 영향이 없었다. IGFBP-5의 zymography에서 정상인과 골감소증 환제어서 180 kDa 크기의 band가 나타났고, gelatin zymography에서 정상 대조군의 경우 66 kDa과 97 kDa 정도의 band가 확인되었고 골감소증 환자의 경우는 69 kDa의 band가 확인되었다.

• 한국식품영양과학회지
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• 제33권7호
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• pp.1133-1138
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• 2004

본 연구는 streptozotocin(STZ)을 투여하여 고혈당이 유발된 생쥐(UM군)에 생지황(Rhemanniae Radix) 전탕액의 투여(5.0 mL/kg/day, RR군)효과를 밝히기 위하여 수행하였다. STZ로 유발된 생쥐에 생지황 전탕액을 6주 동안 구강 투여한 후 혈당과 당내성 검사 및 췌장섬의 면역조직화학 검사를 하였다. 혈당수준은 RH군이 HM군에 비하여 2, 3, 5, 6주에서 유의성 있게 낮았으며, 당내성 검사 또한 RR군이 HM군에 비하여 우수한 결과를 보여 주었다. 6주 후 insulin-양성 5-세포들과 insulin-like growth factor-II 양성 물질들은 HM군에 비하여 RR군에서는 보다 높게 나타났다. HM군에서는 apoptosis 면역반응성 과립들이 췌장섬 전반에 걸쳐 관찰되었으나, RR군에서는 일부 세포들의 핵에서 면역반응성을 보여주었다. HM군에서는 대부분 췌장섬들이 파괴되어 소수 관찰되었으나 RR군은 다수 관찰되었다. 이와 같은 결과로 보아 생지황 전탕액은 STZ로 유발된 손상으로부터 췌장섬을 회복시키는 효과가 있는 것으로 사료된다.

• Fisheries and Aquatic Sciences
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• 제13권3호
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• pp.224-230
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• 2010

Growth hormone (GH) is known as one of the main osmoregulators in euryhaline teleosts during seawater (SW) adaptation. Many of the physiological actions of GH are mediated through insulin-like growth factor-I (IGF-I), and the GH/IGF-I axis is associated with osmoregulation of fish during SW acclimation. However, little information is available on the response of fish IGF-II to hyperosmotic stress. Here we present the first cloned IGF-I and IGF-II cDNAs of marine medaka, Oryzias dancena, and an analysis of the molecular characteristics of the genes. The marine medaka IGF-I cDNA is 1,340 bp long with a 257-bp 5' untranslated region (UTR), a 528 bp 3' UTR, and a 555-bp open reading frame (ORF) encoding a propeptide of 184 amino acid (aa) residues. The full-length marine medaka IGF-II cDNA consists of a 639 bp ORF encoding 212 aa, a 109 bp 5' UTR, and a 416 bp 3' UTR. Homology comparison of the deduced aa sequences with other IGF-Is and IGF-IIs showed that these genes in marine medaka shared high structural homology with orthologs from other teleost as well as mammalian species, suggesting high conservation of IGFs throughout vertebrates. The IGF-I mRNA level increased following transfer of marine medaka from freshwater (FW) to SW, and the expression level was higher than that of the control group, which was maintained in FW. This significantly elevated IGF-I level was maintained throughout the experiment (14 days), suggesting that in marine medaka, IGF-I is deeply involved in the adaptation to abrupt salinity change. In contrast to IGF-I, the increased level of marine medaka IGF-II mRNA was only maintained for a short period, and quickly returned a level similar to that of the control group, suggesting that marine medaka IGF-II might be a gene that responds to acute stress or one that produces a supplemental protein to assist with the osmoregulatory function of IGF-I during an early phase of salinity change.

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