• BMB Reports
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• 제43권2호
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• pp.146-149
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• 2010

Exendin-4 (Ex-4), a peptide secreted from the salivary glands of the Gila monster lizard, can increase pancreatic $\beta$-cell growth and insulin secretion by activating glucagon-like peptide-1 receptor. In this study, we expressed a fusion protein consisting of exendin-4 and the human immunoglobulin heavy chain (Ex-4/IgG-Fc) in E. coli and explored its potential therapeutic use for the treatment of insulin-resistant type 2 diabetes. Here, we show that the Ex-4/IgG-Fc fusion protein induces expression of insulin receptor substrate-2 in rat insulinoma INS-1 cells. Our findings therefore suggest that Ex-4/IgG-Fc overexpressed in E. coli could be used as a potential, long-acting glucagon-like peptide-1 mimetic.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1980년도 학술대회지
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• pp.53-57
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• 1980

Red ginseng powder was administered at a dose of 2.7 g per day for 3 months to 21 diabetic patients who were under the treatment with insulin. It was found that the ginseng powder was effective to 12 patients and ineffective to 9 patients. Based on these clinical results, experiments were carried out to elucidate factors which concerned with improvement of pathological conditions of diabetes mellitus. In the previous symposium, we reported that red ginseng powder contained an anti-lipolytic peptide, or an insulin-like peptide. In the course of purification of the insulin-like peptide in the ginseng, we found another fraction which possessed anti-lipolytic activity. The anti-lipolytic factor of the fraction was purified by gel filtration on Bio Gel P-2 column and Dowex $50W{\times}4$ column chromatography. The character of the finally purified material was examined by thin-layer chromatography, high-speed liquid chromatography and mass spectrometry. With these examinations, the active principle was indentified to be adenosine. Pharmacological significance of these insulin-like substances, the peptide and adenosine, was discussed.

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

• 한국응용곤충학회지
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• 제61권1호
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• pp.85-90
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• 2022

인슐린(insulin)과 insulin-like growth factor-1 (IGF-1)은 척추동물에서 대사, 생장, 수명 등의 여러 생리대사를 조절하는 중요한 호르몬이다. 곤충에서도 IGF-1과 구조적으로 유사한 insulin-like peptide (ILP)들이 존재하며 이들이 곤충 생리 조절에 중요하게 관여함이 밝혀졌다. 이번 총설에서 곤충 ILP 및 초파리(Drosophila melanogaster) 유전체 분석을 통해 척추동물에 존재하는 인슐린 및 IGF-1 수용체 신호전달계와 유사하다고 확인된 ILP 수용체 신호전달계에 대해 설명하고자 한다. 추가적으로, 곤충 체내의 영양 상태에 따라 조절되는 뇌에서의 ILP의 합성과 분비, ILP에 의한 대사의 생리적 조절에 대해 논한다. 또한 ILP가 생장, 발달, 생식, 휴면에 기여하는 바도 논의하고, 마지막으로 ILP 수용체 신호전달계 제어를 통한 해충 방제에의 이용 가능성에 대해 제안하고자 한다.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.20-21
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• 2003

Insulin-like growth factors (IGFs) are mitogenic peptide hormones that regulate embryonic development, postnatal growth and cellular differentiation in vertebrates IGFs are initially translated as pre-pro-peptides and then proteolytically processed to yield the mature IGFs and E-peptides. Like the C-peptide of pro-insulin, the E-peptides of pro-IGFs are generally believed to possess little or no biological activity other than their potential roles in the biosynthesis of the mature IGFs. Like human IGF-1, previous studies in our laboratory showed that the recombinant trout Ea4-peptide of pro-IGF-1 exhibited a dose-dependent mitegenic activity in cultured BALB/3T3 fibroblasts and other non-oncogenic transformed cells (Tian et al., 1999) We have also shown by in vitro and in vivo studies that Ea4-peptide possessed novel anti-tumor activities (Chen et al., 2002, Kuo and Chen, 2002; Kuo and Chen 2003). Recent results of studies conducted in chorionicallantoic membrane of developing chicken embryos revealed that Ea4-peptide of trout pro-IGF-1 also possesses a dose-dependent antiangiogenic activity. Together these results raised the question whether Ea4-peptide of trout pro-IGF-1 may affect heart and blood vessel development and hematopoiesis in fish embryos. (중략)

• BMB Reports
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• 제48권9호
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• pp.501-506
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• 2015

Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition. [BMB Reports 2015; 48(9): 501-506]

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1978년도 학술대회지
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• pp.75-77
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• 1978

It was found that water extract of Panax ginseng strongly inhibited adrenaline-induced lipolysis in isolated fat cells of rat epididymal adipose tissue. An antilipolytic action of the water extract was easily inactivated by treatment with pronase, suggesting that the active principle might be a protein or a peptide. Experiments were designed to purify the antilipolytic substance, or insulin-like substance, of the water extract. The water extract was dialyzed against disti'led water. The outer dialysate was subjected to DEAE-cellulose column chromatography, gelfuaration on sephadex G-50 column, avicel cellulose column chromatography and phospho-cellulose column chromatography, successively. The finally purified substance gave one spot on thin layer chromatography. The molecular weight was found to be around 1000. Experiments are now in progress to elucidate the structure of this insulin-like peptide.

• Journal of Animal Science and Technology
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• 제50권2호
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• pp.177-184
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• 2008

Acid-labile subunit(ALS)는 85-kDa 크기의 당단백질로서 7.5-kDa의 insulin-like growth factor(IGF) 및 40~45-kDa IGF-binding protein-3와 결합하여 150-kDa ternary complex를 형성하는 혈장단백질이다. 선행연구에서 본 연구진은 reverse transcription-polymerase chain reaction(RT-PCR) 방법으로 돼지(porcine) ALS(pALS)의 coding sequence를 합성하여 plasmid vector에 삽입시켜 ‘expression construct’를 제작한 바 있다. 그러나 본 expression construct의 pALS coding sequence에는 PCR error로 추정되는 원인으로 말미암아 2개의 bases에서 mis-sense mutation이 일어난 것이 발견되었다. 본 연구에서는 ‘site-directed mutagenesis’ 방법으로 pALS의 올바른 coding sequence를 합성하여 ‘insert DNA’의 마지막 codon 다음에 ‘His-tag’ sequence가 위치한 pET- 28a(+) plasmid expression vector에 삽입하였다. 본 expression construct는 E. coli BL21(DE3) 세포에서 ‘induction’ 시켰고, 발현된 유전자재조합(recombinant) peptide는 Ni-affinity chromato- graphy로 정제하였다. 이렇게 affinity chro- matography로 정제된 peptide는 SDS-PAGE에서 66kDa 위치에 single band를 나타냄으로써 recombinant pALS의 예상된 질량과 일치하였다. 이상의 결과는 본 연구에서 recombinant pALS peptide가 성공적으로 발현정제되었음을 시사한다.

• Biomolecules & Therapeutics
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• 제24권6호
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• pp.589-594
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• 2016

Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-${\beta}E$ in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-${\beta}E$ subunit of the TGF-${\beta}$ family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.

• Laboraroty Animal Research
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• 제34권4호
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• pp.140-146
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• 2018

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.