• KSBB Journal
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• v.32 no.1
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• pp.71-82
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• 2017

To verify anti-diabetic effect of oligopeptide with His-Pro repeats (mHP peptide), the oligopeptide was first secreted and optimized using the secretion vector, pRBAS with alkaline protease gene promoter and the signal sequence in Bacillus subtilis and directly the anti-diabetic effect of the mHP peptide was investigated in insulinoma cell, RINm5F cell line. The oligopeptide gene was obtained by annealing oligonucleotides with repeated His-Pro sequence and finally was constructed as 18 dipeptides (108 bp and 4.0 kDa) coding gene, named oligopeptide with His-Pro repeats (mHP peptide) to make cyclo(His-Pro) known to be anti-diabetic effects. The region encoding the oligopeptide gene was subcloned into the pRBAS secretion vector (E.coli-Bacillus shuttle vector) after PCR amplification using the designed primers including initiation and termination codons and His tag, named pRBAS-mHP (6.56 kb). To optimize secretion of the oligopeptide, various culture conditions were investigated in Bacillus subtilis LKS. As a result, the secreted oligopeptide was maximally measured (approximately $59.6{\mu}g/mL$) in 3 L batch culture and the highest secretion was achieved at $30^{\circ}C$, PY medium, and carbon sources (particularly barley and glycerol). In the RINm5F cells treated with 2 mM STZ, the oligopeptide treatment (0.1 mg/mL) restored the cell viability (10%) and reduced the nitric oxide (NO) generation (35%) and DNA fragmentation (90%). And also, insulin secretion level was increased to 17% higher than in STZ-treated RINm5F cells. These results suggest that the oligopeptide with His-Pro repeats could be a candidate material for anti-diabetic agent against STZ-induced diabetes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.221-225
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• 2015

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether it can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.

• BMB Reports
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• v.30 no.6
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• pp.379-384
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• 1997

The effects of several ions on the specific activity and isozyme patterns of cellular and secretory isoperoxidases were studied in suspension-cultured cells of rice (Oryza sativa L.). Peroxidase release into the culture medium occurred in the absence of added calcium. The addition of calcium ion greatly stimulated the secretion of cationic isoperoxidases such as C2 and C3 into the medium: a maximum 11 fold increase of secretions occurred in the presence of 5 mM $CaCl_2$, and the secretion was accomplished within 1 hour after the addition of $CaCl_2$. About a 10 fold increase of the peroxidase secretion into the medium did occur with 0. 5% NaCl, whereas cellular isoperoxidase levels were reduced notably. About a 6 fold increase of the specific activity of cellular isoperoxidase was found in 5 mM $NiCl_2$-treated cell, while $NiCl_2$ had no effect on the secretion of peroxidase into the medium. Various concentrations of KCl did not change peroxidase secretion, but 5 mM $ZnCl_2$ reduced peroxidase secretion greatly. The major secretory isoperoxidases stimulated by $CaCl_2$, NaCl and cellulase were composed of cationic isoperoxidases C2 and C3, which were found to be localized in the cell wall of rice by examination of the enzyme in the protoplast. Furthermore, the secretion rates of secretory isoperoxidases were increased rapidly when cellulase was treated in the absence of the osmotic stabilizer of 0.4 M mannitol. These results suggest that the stimulations of secretory isoperoxidase levels seem to be due to the stimulation of secretion into the culture medium of rice.

• Animal cells and systems
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• v.13 no.1
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• pp.17-23
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• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• Korean Journal of Veterinary Research
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• v.15 no.2
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• pp.223-231
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• 1975

In mammals there are two distinct cellular units of the gastric glands which are responsible for the secretion of acid and pepsin respectively, namely, the parietal cells for acid and the peptic or chief cells for pepsin. On the other hand, the bird does net have separate parietal and chief cells in the glandular stomach. There exist only a single cell type in the asian gastric secretory-glands. In spite of this single cell type, however, variation in pepsin and acid secretion can he seen. Present study was conducted to know distribution, secretion and formation of the pepsinogen granules in chicken and rat stomach which observing by light and electron microscope. 1. In chicken, the pepsinogen granules are distributed in all submucosal gland cells and yet there are no distinction of parietal and chief cells. In rat, the pepsinogen granules are distributed in chief cells which lined the lower two-thirds of the gastric tubles and the parietal cells occupy upper third of the tuble. 2. Carbachol markedly stimulates the secretion of pepsinogen granules in chiken and rat, but Histamine is slightly. 3. After Histamine and Carbachol treatment, the pepsinogen granules are formated continuously and reaccmulated as control after 3 to 4 hours.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.383-389
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• 2011

Background: EY-6 is one of the newly synthesized indoledione derivatives to induce tumor cell-specific cell death. In this study, we investigated the mechanism of immunological death induced by EY-6 at mouse colon cancer cell as well as at the normal immune cell represented by dendritic cell. Methods: C57BL/6 mouse syngeneic colon cancer cell MC38 was treated with EY-6, and analyzed by MTT for viability test, flow cytometry for confirming surface expressing molecules and ELISA for detection of cytokine secretion. Normal myeloid-dendritic cell (DC) was ex vivo cultured from bone marrow hematopoietic stem cells of C57BL/6 mice with GM-CSF and IL-4 to analyze the DC uptake of dead tumor cells and to observe the effect of EY-6 on the normal DC. Results: EY-6 killed the MC38 tumor cells in a dose dependent manner (25, 50 and $100{\mu}M$) with carleticulin induction. And EY-6 induced the secretion of IFN-${\gamma}$ but not of TNF-${\alpha}$ from the MC38 tumor cells. EY-6 did not kill the ex-vivo cultured DCs at the dose killing tumor cells and did slightly but not significantly induced the DC maturation. The OVA-specific cross-presentation ability of DC was not induced by chemical treatment (both MHC II and MHC I-restricted antigen presentation). Conclusion: Data indicate that the EY-6 induced tumor cell specific and immunological cell death by modulation of tumor cell phenotype and cytokine secretion favoring induction of specific immunity eliminating tumor cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.660-665
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• 2008

In the present study, we investigated the anti-allergic effect of the water extract of Bopyeoyangyeong-jun(BYJ). To investigate the biological effect of BYJ, We examined cytotoxicity and inflammatory cytokine secretion with RBL-2H3. We examined Cell Viability, ${\beta}$-hexosaminidase, tumor necrosis factor-alpha(TNF-${\alpha}$), interleukin(IL)-4 secretion from RBL-2H3 cell after pre- treatment with Bopyeoyangyeong-jun of 1 mg/ml, 2 mg/ml. RBL-2H3 cell was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. BYJ by itself had no effect on viability of RBL-2H3 cell. We observed that Bopyeoyangyeong-jun reduced ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 secretion in RBL-2H3 cell. Taken together, these results indicate that Bopyeoyangyeong-jun has anti-histamic effect and controls TNF-${\alpha}$, IL-4 secretion on allergic reaction.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.153-160
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• 2012

Panax ginseng has long been used as a traditional herbal medicine. More recently, it has received attention for its anti-diabetic and anti-obesity effects in humans and in animal models of type 2 diabetes. In the present study, we tested the hypoglycemic effects of ginseng berry extract in beta-cell-deficient mice and investigated the mechanisms involved. Red (ripe) and green (unripe) berry extracts were prepared and administered orally (100 or 200 mg/kg body weight) to streptozotocin-induced diabetic mice daily for 10 wk. The body weight was measured daily, and the nonfasting blood glucose levels were measured after 5 and 10 wk after administration. Glucose tolerance tests were performed, and the serum insulin levels were measured. The proliferation of beta-cells was measured in vitro. The administration of red or green ginseng berry extract significantly reduced the blood glucose levels and improved the glucose tolerance in beta-cell deficient mice, with the higher doses resulting in better effects. Glucose-stimulated insulin secretion was significantly increased in berry extract-treated mice compared with streptozotocin-induced diabetic control mice. Treatment with ginseng berry extract increased beta-cell proliferation in vitro. Both red berry and green berry extracts improved glycemic control in streptozotocin-induced diabetic mice and increased insulin secretion, possibly due to increased beta-cell proliferation. These results suggest that ginseng berry extracts might have beneficial effects on beta-cell regeneration.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.469-478
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• 2022

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca²⁺ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.