• 농업과학연구
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• 제41권3호
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• pp.237-243
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• 2014

Human Glucagon like peptide-1 (GLP-1) is an incretin hormone that promotes secretion of insulin. In order to eliminate the formation of the soluble aggregate, Ala19 in GLP-1 was substituted with Thr, resulting in a GLP-1 mutant GLP-1A19T. The gene synthesis of GLP-1A19T and the fusion of 6-lysine tagged ubiquitin gene were accomplished by using the overlap extension polymerase chain reaction. The ubiquitin fused GLP-1A19T (K6UbGLP-1A19T) is expressed as form of inclusion body with little formation of the soluble aggregation in recombinant E. coli. In order to produce K6UbGLP-1A19T in large amounts, fed-batch fermentation was carried out in a pH-stat feeding strategy. Maximum dry cell weight of 87.7 g/L and 20.4% of specific K6UbGLP-1A19T content were obtained. Solid-phase refolding using a cation exchanger was carried out to renature K6UbGLP-1A19T. The refolded K6UbGLP-1A19T aggregated little and was released GLP-1A19T by on-column cleavage with ubiquitin-specific protease-1. The molecular mass of GLP-1A19T showed an accurate agreement with its theoretical molecular mass.

• 대한약침학회지
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• 제23권2호
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• pp.79-87
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• 2020

Objectives: Ginsenosides found in ginseng, and the hydrolysates derived from their conversion, exhibit diverse pharmacological characteristics [1]. These have been shown to include anti-cancer, anti-angiogenic, and anti-metastatic effects, as well as being able to provide hepatic and neuroprotective effects, immunomodulation, vasodilation, promotion of insulin secretion, and antioxidant activity. Therefore, the purpose of this study was to examine how quickly the ginsenosides decompose and what kinds of degradation products are created under physicochemical processing conditions that don't involve toxic chemicals or other treatments that may be harmful. Methods: The formation of ginsenoside-Rg2 and ginsenoside-Rg3 was examined. These demonstrated diverse pharmacological effects. Results: We also investigated physicochemical factors affecting their conversion. The heating temperatures and times yielding the highest concentration of ginsenosides (-Rb1, -Rb2, -Rc, -Rd, -Rf, -Rg1, and -Re) were examined. Additionally, the heating temperatures and rates of conversion of these ginsenosides into new 'ginseng saponins', were examined. Conclusion: In conclusion, obtained provide us with effective technology to control the concentration of both ginsenosides and the downstream converted saponins (ginsenoside-Rg2, Rg3, Rg5, and Rk1 etc.), as well as identifying the processing conditions which enable an enrichment in concentration of these compounds.

• 한국약용작물학회지
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• 제21권5호
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• pp.401-414
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• 2013

Ginsenoside Rg3 (G-Rg3) contained only in red ginseng has been found to show various pharmacological effects such as an anticancer, antiangiogenetic, antimetastastic, liver protective, neuroprotective immunomodulating, vasorelaxative, antidiabetic, insulin secretion promoting and antioxidant activities. It is well known that G-Rg3 could be divided into 20(R)-Rg3 and 20(S)-Rg3 according to the hydroxyl group attached to C-20 of aglycone, whose structural characteristics show different pharmacological activities. It has been reported that G-Rg3 is metabolized to G-Rh2 and protopanaxadiol by the conditions of the gastric acid or intestinal bacteria, thereby these metabolites could be absorbed, suggesting its absolute bioavailability (2.63%) to be very low. Therefore, we reviewed the chemical, physical and biological transformation methods for the production on a large scale of G-Rg3 with various pharmacological effects. We also examined the influence of acid and heat treatment-induced potentials on for the preparation method of higher G-Rg3 content in ginseng and ginseng products. Futhermore, the microbial and enzymatic bio-conversion technologies could be more efficient in terms of high selectivity, efficiency and productivity. The present review discusses the available technologies for G-Rg3 production on a large scale using chemical and biological transformation.

• Annals of Pediatric Endocrinology and Metabolism
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• 제22권1호
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• pp.15-26
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• 2017

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic ${\beta}-cell$ insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide. Now GLP-1R agonists have a variety of dosing-cycle forms to meet the needs of various patients. In this article, we review the physiological features of GLP-1, the effects of GLP-1 on T2D, the features of several GLP-1R agonists, and the therapeutic effect on T2D.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.221-231
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• 2022

Adiponectin (Ad), a 30 kDa molecule, is an anti-diabetic adipokine; although derived from adipose tissue, it performs numerous activities in various other tissues. It binds to its own receptors, namely adiponectin receptor 1(AdipoR1), adiponectin receptor 2 (AdipoR2), and T-cadherin (CDH13). Ad plays several roles, especially as a regulator. It modulates lipid and glucose metabolism and promotes insulin sensitivity. This demonstrates that Ad has a robust correlation with fat metabolism. Furthermore, although Ad is not in direct contact with other tissues, including the skin, it can be delivered to them by diffusion or secretion via the endocrine system. Recently it has been reported that Ad can impact skin cell biology, underscoring its potential as a therapeutic biomarker of skin diseases. In the present review, we have discussed the association between skin cell biology and Ad. To elaborate further, we described the involvement of Ad in the biology of various types of cells in the skin, such as keratinocytes, fibroblasts, melanocytes, and immune cells. Additionally, we postulated that Ad could be employed as a therapeutic target to maintain skin homeostasis.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.95-95
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• 2003

Endocrine factors, such as steroid hormones and growth factors, regulate egg productivity including the number of egg production, egg weight, sexual maturity, and the number of small yellow follicles. Especially, insulin-like growth factor-I (IGF-I) is involved in the regulation of ovulation rate and ovarian follicular development in chickens, and the relationship between IGF-I genotype and egg weight was reported. However, the effect of grwoth factors on egg productivity in Korean Native Ogol Chicken (KNOC) has not been studied. Therefore this study was conducted to identify the relationship among endocrine factors, IGF-I genotypes, and egg productivity. IGF-I genotypes (AA, AB, BB) were represented to 12.6%, 34%, and 53.4%, respectively. AB genotype stimulates the secretion of estradiol and progesterone in serum (30 and 40 week), regulates growth and proliferation of follicles at 60 weeks, and is positively associated with the number of small yellow follicles. Therefore, these results suggest that there are possibility to IGF-I genotypes for a genetic marker in egg productivity of KNOC.

• 대한의생명과학회지
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• 제28권4호
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• pp.322-326
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• 2022

The purpose of this study was to develop hydrolysate from silkworm (Cudrania Silkworm Fibroin Peptide; CSFP), a food containing components for improving blood vessel health. In general, Cudrania tricuspidata leaves contain about 5 times more rutin and 25 times more dihydroquercetin than mulberry leaves. 1-Deoxynojirimycine (1-DNJ), dihydroquercetin and rutin inhibit the activity of carbohydrate-digesting enzymes, inhibit blood lipid peroxidation, and regulate insulin secretion, which helps blood vessels to be healthy. When the diet-controlled silkworm was enzymatically hydrolyzed, it was confirmed that rutin content was about 8 times higher than that of the in general silkworm as a control. In the silkworm hydrolysate, CSFP, developed as a final food material, the active ingredients were 65 mg/kg for rutin, 3,328 mg/kg for DNJ, 0.43 mg/kg for dihydroquercetin, and 82,624 mg/kg for total polyphenol, which was confirmed through LC-MS/MS analysis. In conclusion, it was found that silkworms fed with C. tricuspidata leaves as a diet had more active components that can help control blood sugar and improve blood vessel health than silkworms fed with mulberry leaves.

• Fisheries and Aquatic Sciences
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• 제27권1호
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• pp.17-22
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• 2024

Diabetes Mellitus (DM) is a major health issue increasing worldwide. Currently, nearby half a billion people have diabetes. Two major types of DM that type 1 and type 2-DM have different etiologies but feature a crucial common pathological transition into dysfunction of pancreatic β-cells and consequently leading hyperglycemia and finally go into DM. Therefore, maintaining of β-cells such as preventing β-cells degeneration, and promoting β-cells regeneration and proliferation will be essential approaches in prevention and/or treatment of DM. There are many reports that various types of seaweed control metabolic diseases such as obesity, high blood pressure, and blood sugar control. However, no new drug candidates have been developed yet. Additionally, although seaweed has excellent blood sugar control effects, there is no evidence that it directly proliferates or regenerates beta cells. Therefore, we studied on the promotion of β-cell regeneration by a seaweed, Polysiponia morrowii extract (PME) which preserves β-cells and maintains its function. As a result, it was confirmed that PME directly promotes the proliferation of pancreatic islet β-cells with insulin secretion function in in vivo. Therefore, PME shows potential as a candidate for β-cell regeneration that may play a fundamental role in the treatment of diabetes.

• 한국가축번식학회지
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• 제23권2호
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• pp.105-111
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• 1999

본 연구는 한우 난소의 황체세포를 분리ㆍ체외배양하여 progesterone 과 IGF-I 분비기능에 대한 비장세포의 첨가효과를 검토하여 난소기능에 대한 기초정보를 제공하는데 있다. 도축장에서 도축되는 한우 난소로부터 황체를 분리ㆍ효소처리하여 LLC 와 SLC (1$\times$$10^{6}$ cells/$m\ell$)를 회수하였으며 10% FCS와 antibiotic가 첨가된 D-MEM 배양액에 24 시간 체외배양하였다. 비장세포는 성숙한 거세한우의 비장에서 회수하여 5%, 10% 및 20%를 황체세포에 각각 첨가하여 공배양하였다. 황체일령별 조직내 progesterone 농도는 발정주기 중 중기황체 (CL-3)가 유의적으로 높았다. 비장세포를 5%, 10% 및 20%를 각각 황체세포에 첨가하여 배양한 결과, 배양액 중의 progesterone 농도는 대조구에 비해 유의적인 차이가 발견되지 않았으나 LH(100ng/$m\ell$) 첨가구와 비장세포 5%, 10%, 20% 첨가와 함께 LH 를 각각 공배양구에서 대조구(LH＋BP)에 비해 유의적 (p＜0.05)으로 높은 progesterone 분비를 나타내었다. 한편, 황체세포의 체외배양에 있어서 IGF-I은 일정하게 분비하였으나 비장세포와 LH＋비장세포 5%, 10% 및 20%와의 공배양은 대조구에 비해 큰 차이가 없었으나 LH 단독처리구만이 대조구에 비해 유의적으로 (p＜0.05) 높은 수준을 보였다. 이상의 결과로, 비장세포는 황체세포에 작용하여 LH 의 progesterone 분비기능을 촉진시킴으로서 황체세포의 progesterone 분비를 촉진하는 기능이 있으나 IGF-I의 분비기능은 없는 것으로 사료된다.

• 한국영양학회:학술대회논문집
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• 한국영양학회 1995년도 추계학술대회 초록
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.