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Myung Jun Kim  (Kim MJ) 4 Articles
Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus.
Ji Won Kim, Dong Sik Ham, Heon Seok Park, Yu Bai Ahn, Ki Ho Song, Kun Ho Yoon, Ki Dong Yoo, Myung Jun Kim, In Kyung Jeong, Seung Hyun Ko
Korean Diabetes J. 2009;33(3):185-197.   Published online June 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.3.185
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AbstractAbstract PDF
BACKGROUND
Vascular endothelial growth factor (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF treatment has any effects on the pancreatic islets in an animal model of type 2 diabetes mellitus. METHODS: Anti-VEGF peptide (synthetic ATWLPPR, VEGF receptor type 2 antagonist) was injected into db/db mice for 12 weeks. We analyzed pancreatic islet morphology and quantified beta-cell mass. Endothelial cell proliferation and the severity of islet fibrosis were also measured. VEGF expression in isolated islets was determined using Western blot analysis. RESULTS: When anti-VEGF was administered, db/db mice exhibited more severe hyperglycemia and associated delayed weight gain than non-treated db/db mice. Pancreas weight and pancreatic beta-cell mass were also significantly decreased in the anti-VEGF-treated group. VEGF and VEGF receptor proteins (types 1 and 2) were expressed in the pancreatic islets, and their expression was significantly increased in the db/db group compared with the db/dm group. However, the elevated VEGF expression was significantly reduced by anti-VEGF treatment compared with the db/db group. The anti-VEGF-treated group had more prominent islet fibrosis and islet destruction than db/db mice. Intra-islet endothelial cell proliferation was also remarkably reduced by the anti-VEGF peptide. CONCLUSION: Inhibition of VEGF action by the VEGF receptor 2 antagonist not only suppressed the proliferation of intra-islet endothelial cells but also accelerated pancreatic islet destruction and aggravated hyperglycemia in a type 2 diabetes mouse model. Therefore, the potential effects of anti-VEGF treatment on pancreatic beta cell damage should be considered.
Pancreatic Stellate Cell Activation by High Glucose and Its Effect on Angiotensin II.
Seung Hyun Ko, Oak Kee Hong, Min Kyung Lee, Eun He Park, Sung Soo Lee, Yu Bai Ahn, Ki Ho Song, Bong Yun Cha, Ho Young Son, Myung Jun Kim, In Kyung Jung, Kun Ho Yoon
Korean Diabetes J. 2005;29(4):304-314.   Published online July 1, 2005
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AbstractAbstract PDF
BACKGROUND
Pancreatic stellate cells (PSCs) are known to be related to pancreatic inflammation and fibrosis, and are the result of extracellular matrix(ECM) protein synthesis. Recent studies have shown that blockade of the renin-angiotensin system (RAS) attenuated pancreatic inflammation and fibrosis. However, there is little data relating to high glucose (HG) and its effects on PSCs. We investigated the effects of HG on ECM protein and angiotensin II(AT II) in PSCs. METHODS: Isolated PSCs were cultured in HG(D-glucose 5.5(LG), 27.8 mM(HG)) medium. The levels of AT II and TGF-beta were measured using radioimmunoassay, and the AT II-stained cells counted. RT-PCR for the AT II receptor subtypes and Western blot analyses for the expressions of ECM proteins, such as connective tissue growth factor(CTGF) and collagen type IV, were performed. The AT II receptor antagonist, candesartan(10micrometer), and angiotensin converting enzyme inhibitor, ramiprilat(100nM) treatedments were also used. RESULTS: The thymidine uptake of the PSCs increased 4 times in the HG culture. The AT II levels(LG vs. HG, 17.1+/-4.9 vs. 36.0+/-.2pg/mL, P<0.05) and AT II-stained PSCs (LG vs. HG, 22.5+/-2.0 vs. 39.3+/-11.0%, P<0.05) were significantly increased after 6 hrs under HG conditions. The TGF-beta concentration was also significantly higher under HG conditions(LG vs. HG, 436.3+/-69.0 vs. 1115.1+/-434.0pg/mL, P<0.05) after 72 hrs. After 72 hrs, the protein expressions of CTGF and collagen type IV under HG conditions were significantly increased and effectively attenuated by the candesartan and ramiprilat treatments. CONCLUSION: A high glucose concentration could significantly increased PSCs proliferation, which also correlated with the AT II production. Consequently, PSCs proliferation was caused by HG induced ECM protein synthesis, and was attenuated by the AT II receptor antagonist. Therefore, pancreatic inflammation and fibrosis could be aggravated by hyperglycemia, and AT II might play an important role in the pathogenesis.
The Role of cAMP/PKA Activation on Exendin-4-Induced Cyclin D1 Expression in INS-1 Cell.
Gyeong Ryul Ryu, Jung Hoon Kang, Hwa In Jang, Seung Hyun Ko, In Kyung Jeong, Duck Joo Rhie, Shin Hee Yoon, Sang June Hahn, Yang Hyeok Jo, Myung Suk Kim, Myung Jun Kim
Korean Diabetes J. 2005;29(4):295-303.   Published online July 1, 2005
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AbstractAbstract PDF
BACKGROUND
Glucagon-like peptide-1(GLP-1) and exendin-4(EX-4) have been known to induce pancreatic islet proliferation and increases in the betacell mass. Cyclin D1 is a key protein responsible for the entry of the G into the S phase, thereby contributing to cell proliferation. Therefore, the effect of EX-4 on the expression of cyclin D1 in INS-1 cells, a rat pancreatic betacell line, was investigated. The involvement of either mitogen-activated protein kinases(MAPKs) or cyclic adenosine 5'-monophosphate/protein kinase A(cAMP/ PKA) in the EX-4-induced cyclin D1 expression was also examined. METHODS: INS-1 cells were treated with EX-4 (10 nM), and the cyclin D1 protein levels then determined by Western blot. To investigate the involvement of MAPKs in the EX-4- induced cyclin D1 expression, either a combined treatment of MAPKs inhibitors or transient transfection of extracellular signal-regulated kinase-1 (ERK1) was performed. The effect of cAMP on the EX-4-induced cyclin D1 expression was also examined by treatments with forskolin, an adenylyl cyclase activator, and H-89, a PKA inhibitor. RESULTS: EX-4 increased the expression of cyclin D1 protein in a dose-dependent manner. Although EX-4 induced phosphorylation of ERK1/2, the treatment with PD 98059 or the overexpression of ERK1 had no effect on the EX-4-induced cyclin D1 expression. However, forskolin significantly induced the expression of cyclin D1, whereas the pretreatment of H-89 inhibited the EX-4-induced cyclin D1 expression. CONCLUSION: These results suggest that EX-4 induce cyclin D1 expression in INS-1 cells via cAMP/PKA pathway, but this is not due to ERK activation.
The Inhibitory Effect of Epicatechin on IL-1beta -induced iNOS Expression and NO Production in RINm5F Cell.
Gyeong Ryul Ryu, Do Sik Min, Duck Joo Rhie, Shin Hee Yoon, Sang June Hahn, Myung Suk Kim, Yang Hyeok Jo, Myung Jun Kim
Korean Diabetes J. 2003;27(6):456-466.   Published online December 1, 2003
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AbstractAbstract PDF
BACKGROUND
Interleukin-1beta (IL-1beta ) stimulates the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO), lead to NO-mediated insulin, which produces cell damage. Within these signal pathways, nuclear factor-kappaB (NF-kappaB) activation is crucial, with many IL-1beta -sensitive genes containing NF-kappaB binding sites in their promoter regions. The inhibitory effect of (-)epicatechin (EC), an antioxidant agent, on IL-1beta -induced NF-kappaB activation, and the subsequent iNOS expression in RINm5F cells, were examined. METHODS: RINm5F cells were pretreated with EC (0.8 mM), and then cultured with IL-1beta (10U/mL), and the iNOS mRNA and protein levels then determined by Northern and Western blots, respectively. The production of NO was measured as nitrite in the culture supernatant. The protein levels of the inhibitor of nuclear factor kappaB (IkappaB) and NF-kappaB DNA binding activity were determined by Western blot and electrophoretic mobility shift assay, respectively. Also, the promoter activity following transient transfection of the iNOS promoter-luciferase reporter genes into the cells were tested. RESULTS: EC was found to significantly reduce the IL-1beta -induced NO production, and iNOS protein and mRNA levels, and also blocked the IL-1beta -induced IkappaB protein degradation, NF-kappaB activation and iNOS promoter activity. CONCLUSION: These results suggest that EC inhibits the IL-1beta -induced iNOS expression in RINm5F cells, by interfering with the binding of the NF-kappaB to the iNOS promoter, thereby inhibiting the induction of iNOS transcription.

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