• 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.

• Nutrition Research and Practice
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• 제15권5호
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• pp.568-578
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• 2021

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 ㎍/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor 𝛄 (PPAR𝛄), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS: The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

• Asian-Australasian Journal of Animal Sciences
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• 제8권1호
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• pp.51-58
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• 1995

To examine whether colostral growth factors are transferred to the general circulation, concentrations of plasma cortisol, insulin, prolactin, growth hormone, insulin-like growth factors(IGFs) -I and -II, IGF-binding proteins(IGFBPs) and total protein were measured in newborn calves fed colostrums, milk of milk replacer before and after feeding at 12 h intervals during the first two days after birth. Plasma protein concentrations increased with time after than in milk- or milk replacer-fed calves. The mean protein concentration was greater in colostrum-fed than in milk- or milk replacer-fed calves. Plasma cortisol levels transiently declined after each feeding regardless of the type of diet, while insulin levels tended to increase. Mean concentrations of these hormones did not differ between dietary groups, nor did they change with time after birth. Plasma concentrations of prolactin and growth hormone did not differ between dietary groups and also did not change with time after birth or after feeding. Concentrations of IGF-I and IGF-II transiently increased at the second feeding period, but these, as well as plasma IGFBP profiles, were not different between groups or before and after feeding. Results did not indicate significant transfer of colostral growth factors across the newborn ruminant small intestine.

• Clinical and Experimental Pediatrics
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• 제51권12호
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• pp.1329-1335
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• 2008

목 적: 저자들은 한국 소아발육 표준치를 이용하여 25-50백분위수에 속하는 정상대조군 환자들의 혈중 I형 인슐린 양 성장인자(IGF-I)와 인슐린 양 성장인자 결합단백-3 (IGFBP-3) 농도의 SD치를 이용하여, 성장호르몬 결핍증을 진단하는데 있어서 검색검사로서의 진단적 유용성에 대한 분석을 시도하였다. 방 법: 성장호르몬 결핍증 환아 31명, 정상대조군 230명(남아 129명, 여아 101명)을 대상으로 하였다. 성장호르몬 결핍증 환자는 완전 결핍증 14명(남아 12명, 여아 2명), 부분 결핍증 17명(남아 9명, 여아 8명) 이었다. 연령분포는 7세에서 15세 사이였다. IGF-I은 RIA 방법으로, IGFBP-3는 IRMA 방법으로 측정하였다. 결 과: ROC 분석을 통해 얻어진 가장 가능성이 높은 절단치는 정상대조군에서 얻어진 혈중 농도의 -1 표준 편차에 해당하는 값과 유사하였다. 이를 토대로 하여 정상키를 가진 대조군의 혈중 IGF-I 농도의 -1 표준편차 값을 기준 절단치로 잡아 7-9세군, 10-12세군, 13-14세군 각각에서의 성장호르몬 결핍증의 민감도와 특이도를 계산하였을 때 민감도는 87.5-100%였고 특이도는 80-84.6%로 비슷하게 나타났다. 혈중 IGFBP-3는 민감도는 58.7-85.7%로 다소 차이가 많았고 특이도는 79.2-85.5%로 유사하였다. 전체 연령군을 대상으로 한 혈중 IGF-I의 진단적 정확도는 완전결핍 군에서 78.5%, 불완전결핍 군에서는 94.1%였다. 혈중 IGFBP-3의 진단적 정확도는 완전결핍 군에서 83.3%, 불완전결핍 군에서는 76.5%였다. 결 론: 성장호르몬 결핍증을 진단하기 위해서 외래에서 시행하는 일회성 검색검사로 혈중 IGF-I 및 IGFBP-3농도의 측정은 신체계측, 방사선학적 검사법등과 함께 유용하게 사용될 수 있을 것으로 판단되며, 본 연구에서는 절단치를 대조군으로부터 얻어진 혈중 평균농도치의 -1 표준 편차 값으로 잡았을 때 비교적 만족할 만한 결과를 얻었다고 생각한다.

• 대한수의학회지
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• 제37권2호
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• pp.301-310
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• 1997

Diabetes mellitus is associated with a wide range of pathophysiological in the kidney. This study was designed to examine the effects of high glucose concentration on IGF-I binding and glucose transporters in renal proximal tubule cells. The results were as follows : The binding of $^{125}I-IGF-I$ reached the peak at the 30 minutes and gradually decreased by the time dependent manner. The binding of $^{125}I-IGF-I$ was inhibited by the unlabelled IGF-I($10^{-14}{\sim}10^{-8}M$) in a concentration dependent manner. The relative affinity of IGF-I receptor for IGF-I, IGF-II and insulin exhibited typical type 1 binding(IGF-I > insulin > IGF-II). However IGF-II did not compete for the cultured cell membrane $^{125}I-IGF-I$ binding site at $10^{-14}{\sim}10^{-8}M$. Under optimal conditions, IGF-I binding to the membranes from 5mM and 20mM glucose treated cells was analyzed. It was found that 20mM glucose treated cells exhibited higher binding activity for IGF-I. In order to further substantiate this increase in IGF-I binding sites, we performed affinity-labelling studies. The cross-linked cell membrane subjected to SDS-PAGE; labelled material was detected by autoradiography. 20mM glucose treated cells exhibited higher levels. The initial rate of $methyl-{\alpha}-D-glucopyranoside({\alpha}-MG)$ uptake was significantly lower($74.41{\pm}6.71%$) in monolayers treated with 20mM glucose than those of 5mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. IGF-I significantly increased ${\alpha}-MG$ uptake in both 5mM and 20mM glucose treated cells. However, 3-O-MG uptake was not affected by IGF-I in both conditions. In conclusion, 20mM glucose increased binding sites of $^{125}I-IGF-I$, inhibited Na/glucose cotransporter activity. But 20mM glucose did not change facilitated glucose transporter.

• Tuberculosis and Respiratory Diseases
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• 제47권5호
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• pp.618-628
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• 1999

연구배경: 세포성장은 세포증식과 세포죽음의 균형에 의해 이루어 진다. 세포성장에 관여하는 여러 growth factor증 IGF-I은 IGF-IR와 결합하여 세포증식을 유발하는 mitogen으로 알려져 있다. 또한 IGF-I에 결합하는 IGFBPs중에 IGFBP-3는 혈액내에 가장 많은 carrier protein으로, IGF-I과 결합하여 IGF-I의 세포증식 효과를 증가 혹은 억제시킨다. 방 법: 3T3 fibroblast 세포를 이용하여 IGF-I과 IGF-IR transcripts를 northern blot으로 확인하고, IGF-I에 의한 mitogenic effect를 MTT assay 및 $^3H$-thymidine incorporation test로 관찰하고, IGF-I의 receptor인 IGF-IR의 활성화를 보기 위해 intracellular $\beta$-subunit의 tyrosine kinase domain의 phosphorylation을 western blot으로 관찰하였다. 또한 IGFBP-3가 3T3 세포에서 mitogenic effect에 미치는 영향을 보기 위해 anti-IGFBP-3와 ${\alpha}IR_3$을 단독 및 병용투여하여 관찰하였다. 결 과: 3T3 세포는 IGF-I와 IGF-IR의 mRNA expression을 보였으며, IGF-I을 투여시 IGF-IR의 intracelluar cytoplasmic protein인 $\beta$-subunit의 tyrosine kinase domain을 phosphorylation시켜 활성화시키며, 5%, 1% serum-containing media에서 세포증식을 보였으나, serum-free media에서는 세포증식을 보이지 않았다. 또한 anti-IGFBP-3 투여와 ${\alpha}IR_3$과 anti-IGFBP-3를 병용투여시는 세포종식이 각각 2배이상 증가하였으나, ${\alpha}IR_3$을 4시간 전처치후 ${\alpha}IR_3$과 anti-IGFBP-3를 병용투여시는 anti-IGFBP-3에 의한 세포종식이 보이지 않은 것으로 보아 IGF -I/IGFBP-3 결합에서 분리되는 free IGF-I어l 의해 세포증식이 유도된 것으로 생각된다. 결 론: IGF-I은 IGF-IR를 phosphorylation시켜 mitogenic effect를 보이며, IGFBP-3는 IGF-I의 mitogenic effect를 억제하는 것으로 생각된다.

• 대한의생명과학회지
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• 제15권4호
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• pp.301-307
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• 2009

Whole-body insulin resistance results largely from impaired insulin-stimulated glucose disposal in skeletal muscle. Our previous studies using differential display and quantitative real-time RT-PCR have shown that a novel cDNA band (DD23) had a higher level of expression in insulin resistant skeletal muscle and it was correlated with whole-body insulin action, independent of age, sex, and percent body fat. In this study, we cloned and characterized DD23. The DD23 sequence is part of the 3'UTR region of the RNA binding motif, single stranded interacting protein (RBMS3). We have cloned the full length cDNA for RBMS3 and identified two splice variants. These variants named DD23-L and DD23-S have 15 and 14 exons respectively and differ from RBMS3 in the 3'UTR significantly. Northern blot analyses showed that an ~8.8 kb mRNA transcript of DD23 was predominantly expressed in skeletal muscle and to a lesser extent in placenta, but not in heart, brain, lung, liver, or kidney, unlike RBMS3. Elevated expression levels of these novel alternatively spliced variants of RBMS3 in skeletal muscle may play a role in whole body insulin resistance.

• Biotechnology and Bioprocess Engineering:BBE
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• 제6권2호
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• pp.144-149
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• 2001

For the production and purification of a single chain human insulin precursor, four types of fusion peptides $\beta$-galactosidase (LacZ), maltose binding protein (MBP), glutathione-S-transferase (GST), and (His)(sub)6-tagged sequence (HTS) were investigated. Recombinant E. coli harboring hybrid genes was cultivated at 37$\^{C}$ for 1h, and gene induction occurred when 0.2mM of isopropyl-D-thiogalactoside (IPTG) was added to the culture broth, except for E. coli BL21 (DE3) pLysS harboring a pET-BA cultivation with 1.0mM IPTG, followed by a longer than 4h batch fermentation respectively. DEAE-Sphacel and Sephadex G-200 gel filtration chromatography, amylose affinity chromatography, glutathione-sepharose 4B affinity chromatography, and a nickel chelating affinity chromatography system as a kind of immobilized metal ion affinity chromatography (IMAC) were all employed for the purification of a single chain human insulin precursor. The recovery yields of the HTS-fused, GST-fused, MBP-fused, and LacZ-fused single chain human insulin precursors resulted in 47%, 20%, 20%, and 18% as the total protein amounts respectively. These results show that a higher recovery yield of the finally purified recombinant peptides was achieved when affinity column chromatography was employed and when the fused peptide had a smaller molecular weight. In addition the pET expression system gave the highest productivity of a fused insulin precursor due to a two-step regulation of the gene expression, and the HTS-fused system provided the highest recovery of a fused insulin precursor based on a simple and specific separation using the IMAC technique.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 2004년도 제56차 추계 학술대회 연제집
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• pp.34.1-34.1
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• 2004

• 한국수산과학회지
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• 제33권6호
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• pp.541-545
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• 2000

알긴산은 3T3-L1 세포의 분화를 억제하였다. 3T3-L1 세포의 분화를 촉진시키는 인자로 밝혀진 IGF-I과 insulin을 이용하여 알긴산의 분화에 미치는 영향을 검토한 결과, 알긴산은 insulin의 분화촉진작용을 특이적으로 억제하였다. 본 연구는 알긴산을 이용하여 알긴산의 지질 감소효과를 세포의 수준에서 검증하고자 하였다는 점에서 그 의의가 있으며, 이에 알긴산의 분화억제효과가 일어나는 메카니즘에 관한 연구가 있어야 할 것으로 생각된다.