Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Author index

Page Path
HOME > Browse > Author index
Search
Ji Won Kim  (Kim JW) 7 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
  • 2,283 View
  • 25 Download
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.
The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells.
Ji Hyun Kim, Ji Won Kim, Sung Yoon Jeon, Heon Seok Park, Dong Sik Ham, Young Hye You, Seung Hwan Lee, Jae Hyoung Cho, Mi Ja Kang, Kang Woo Lee, Hyuk Sang Kwon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Sung Koo Kang, Ho Young Son
Korean Diabetes J. 2008;32(2):102-111.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.102
  • 2,582 View
  • 31 Download
AbstractAbstract PDF
BACKGROUND
Insulin receptor substrate 2 (IRS-2) is a key regulator of beta cell proliferation and apoptosis. This study was aimed to investigate effect of the glucolipotoxicity on apoptosis in INS-1 cell, and the effect of Exendin-4, a GLP-1 receptor agonist, on IRS-2 expression in the glucolipotoxicity induced INS-1 cell. The goal was to discover the new action mechanism and function of Exendin-4 in beta cell apoptosis. METHOD: INS-1 cells were cultured in glucolipotoxic condition for 2, 4 or 6 days and were categorized as G groups. Another group in which 50 nM Exendin-4 was added to INS-1 cells, cultured in glucolipotoxic condition, were named as Ex-4 groups. We investigated the expression of IRS-2 by RT-PCR, phosphorylated IRS-2 and phosphorylated Akt protein levels by western blot. We measured the apoptosis ratio of INS-1 cell in glucolipotoxic condition by TUNEL staining in both groups. RESULT: IRS-2 expression of INS-1 cells decreased with correlation to the time of exposure to glucolipotoxic condition. pIRS-2 and pAkt protein levels decreased in the similar pattern in glucolipotoxicity group. However, this effect of glucolipotoxicity on INS-1 cell was inhibited by the Exendin-4 treatment. In the Ex-4 groups, IRS-2 expression, pIRS-2 and pAkt protein levels remained at the similar level to low glucose condition state. Also, apoptosis induced by glucolipotoxicity was suppressed by Exendin-4 treatment significantly. CONCLUSION: We showed that the long-term treatment of Exendin-4 inhibited the apoptosis of beta cells significantly in glucolipotoxic condition and that this effect of Exendin-4 was related with IRS-2 and Akt among the beta cell's intracellular signal transduction pathway.
AICAR Reversed the Glucolipotoxicity Induced beta-cell Dysfunction through Suppression of PPAR-gamma-coactivator-1 (PGC-1) Overexpression.
Hyuk Sang Kwon, Ji Won Kim, Heon Seok Park, Seung Hyun Ko, Bong Yun Cha, Ho Young Son, Kun Ho Yoon
Korean Diabetes J. 2007;31(4):310-318.   Published online July 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.4.310
  • 2,015 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
Glucolipotoxicity plays an important role in the progression of type 2 diabetes mellitus via inducing insulin secretory dysfunction. Expression of insulin gene in pancreatic beta cell might be regulated by AMP-activated protein kinase (AMPK), which is recognized as a key molecule of energy metabolism. We studied the effects of AMPK on glucolipotoxicity-induced beta-cell dysfunction by suppression of PPAR-gamma-coactivator-1 (PGC-1) in vitro and in vivo. Method: Glucolipotoxicity was induced by 33.3 mM glucose and 0.6 mM (palmitate and oleate) for 3 days in isolated rat islets. Messenger RNA (mRNA) expressions of beta-cell specific gene like insulin, BETA2/NeuroD and PGC-1 induced by glucolipotoxic condition and their changes with 5-aminoimidazole-4-carboxy-amide-1-D-ribofuranoside (AICAR) treatment were investigated using RT-PCR. We also examined glucose stimulated insulin secretion in same conditions. Furthermore, SD rats were submitted to a 90% partial pancreatectomy (Px) and randomized into two groups; Ad-GFP-infected Px rats (n = 3) and Ad-siPGC- 1-infected Px rats (n = 3). Then, the Px rats were infected with Ad-GFP or Ad-siPGC-1 (1 x 10(9) pfu) via celiac artery. After 12 days of viral infection, we measured body weight and performed the intraperitoneal glucose tolerance test (IP-GTT). RESULTS: Glucolipotoxicity resulted in blunting of glucose-stimulated insulin secretion, which was recovered by the AICAR treatment in vitro. Suppression in their expressions of insulin and BETA2/NeuroD gene by glucolipotoxic condition were improved with AICAR treatment. However, PGC-1alpha expression was gradually increased by glucolipotoxicity, and suppressed by AICAR treatment. Overexpression of PGC-1 using an adenoviral vector in freshly isolated rat islets suppressed insulin gene expression. We also confirmed the function of PGC-1 using an Ad-siPGC-1 in vivo. Direct infection of Ad-siPGC-1 in 90% pancreatectomized rats significantly improved glucose tolerance and increased body weight. CONCLUSION: AMPK could protect against glucolipotoxicity induced beta-cell dysfunction and the suppression of PGC-1 gene expression might involved in the insulin regulatory mechanism by AMPK.
PDX-1/VP16 Overexpression Induce the Transdifferentiation of Canine Adult Pancreatic Cells into Beta-cells.
Young Hye You, Sun Cheol Park, Seung Hwan Lee, Heon Seok Park, Dong Sik Ham, Marie Rhee, Ji Won Kim, Ki Ho Song, Kun Ho Yoon
Korean Diabetes J. 2007;31(1):51-62.   Published online January 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.1.51
  • 2,001 View
  • 20 Download
  • 3 Crossref
AbstractAbstract PDF
BACKGROUND
A major obstacle of islet transplantation is an inadequate supply of insulin-producing tissue. Ad-PDX-1/VP16 overexpression and Exendin-4 treatment have been proved the effects on differentiation and proliferation of pancreatic stem cells. But, the study is insufficient using adult animal pancreatic stem cells. METHODS: Pancreatic cells were prepared from the non-endocrine fraction of canine pancreases. This cells were cultivated free floating state and monolayer culture after dispersion. The floating pancreatic cells were transplanted under the kidney capsule of normoglycaemic nude mice. The dispersed pancreatic cells were infected with Ad-PDX-1/VP16 or Ad-GFP. After infection, those cells were transplanted of nude mice. After transplantation, mice were treated with either 1 nmol/kg exendin-4 or saline solution by intraperitoneal injection for 10 days. RESULTS: The relative volume of the beta-cells in the grafts of the free floating cultured pancreatic cells were 23.4 +/- 13.1% at two weeks and 5.2 +/- 2.0% at eight weeks. At two weeks after transplantation, the relative volume of insulin-positive cells in the grafts of dispersed pancreatic cells were 28 +/- 5.7%, 20.5 +/- 0.7% and 31 +/- 1.4% in control, GFP and PDX-1/VP16 treated groups respectively. At eight weeks after transplantation, the relative volume of insulin-positive cells in the grafts were 11.8 +/- 5.9%, 8 +/- 7.3% and 16.6 +/- 7.4% in control, GFP and PDX-1/VP16 treated groups respectively. Exendin-4 treatment didn't show any additive effects on transdifferentiation of pancreas stem cell into beta-cells. CONCLUSION: The expansion and transdifferentiation were not observed after the transplantation of the free floating cultured pancreatic cells. PDX-1/VP16 overexpression induces the transdifferentiation of adult pancreatic cells into beta-cells. However Exendin-4 treatment hasn't any effects on the expansion and transdifferentiation of the cells in the grafts.

Citations

Citations to this article as recorded by  
  • Generation of Functional Insulin-Producing Cells from Neonatal Porcine Liver-Derived Cells by PDX1/VP16, BETA2/NeuroD and MafA
    Dong-Sik Ham, Juyoung Shin, Ji-Won Kim, Heon-Seok Park, Jae-Hyoung Cho, Kun-Ho Yoon, Kathrin Maedler
    PLoS ONE.2013; 8(11): e79076.     CrossRef
  • Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells
    Young-Hye You, Dong-Sik Ham, Heon-Seok Park, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
    Diabetes & Metabolism Journal.2011; 35(2): 119.     CrossRef
  • Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
    Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
    Korean Diabetes Journal.2009; 33(6): 475.     CrossRef
Inducible Nitric Oxide Synthase (iNOS) Expression in the Hypoxic Injury to Pancreatic Beta (MIN6) Cells.
Seung Hyun Ko, Seung Bum Kim, Kyung Ryul Ryu, Ji Won Kim, Yu Bai Ahn, Sung Dae Moon, Sung Rae Kim, Jung Min Lee, Hyuk Snag Kwon, Kun Ho Yoon, Ki Ho Song
Korean Diabetes J. 2006;30(5):336-346.   Published online September 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.5.336
  • 2,174 View
  • 20 Download
AbstractAbstract PDF
BACKGROUND
Islet transplantation is an alternative potential strategy to cure type 1 diabetes mellitus. However, two or more donors are usually needed for one recipient because a substantial part of the graft becomes nonfunctional due to several factors including hypoxia. Though hypoxic exposure of pancreatic beta cells has been reported to induce apoptotic cell death, the molecular processes involved in hypoxia-induced cell death are poorly understood. In type I diabetes, Nitric Oxide (NO) is known as an important cytokine, involved in the pathogenesis of beta cell dysfunction. Pancreatic beta cells are sensitive to the induction of inducible nitric oxide synthase (iNOS) when stimulated by TNF-a or IL-1beta. But contribution of iNOS in response to hypoxia is not yet fully understood. METHODS: Mouse insulinoma cells (MIN6) were incubated in an anaerobic chamber (75% N2/15% CO2/5% H2) for up to 12 hours. Cell viability was measured after AO/PI staining. Caspase-3 activation was also determined using Western blot analysis. Nitric Oxide (NO) release into culture medium was measured using a Griess reagent. The expression of iNOS and PDX-1 mRNA and iNOS protein was examined using real time PCR and Western blot analysis. RESULTS: Marked cell death was observed within 6 hours after hypoxic exposure of MIN6 cells (control, < 5%; 2 hr, 11.0+/-7.6%; 6 hr, 46.2+/-12.8%, P < 0.05). Immunoreactivity to activated caspase-3 was observed at 2, 4 and 6 hrs. NO production was increased in a time dependent manner. Expression of iNOS mRNA and protein was significantly increased at 4 and 6 hour after hypoxia. iNOS expression was confirmed by immunostaining. Of note, Pdx-1 mRNA expression was markedly attenuated by hypoxic treatment. Pretreatment with a selective iNOS inhibitor, 1400 W, significantly prevented beta cell death induced by hypoxic injury. CONCLUSION: Our data suggest that iNOS-NO play an important role in hypoxic injury to MIN6 cells. Therefore, iNOS-NO might be a potential therapeutic target for improving engraftment of the transplanted islets and suppression of iNOS would be helpful for prevention of beta cells damage to hypoxic injury.
The effects of mixed chimerism conducted by natural killer cell depletion with non myeloablation on islet allograft rejection.
Heon Seok Park, Seok Goo Cho, Chung Gyu Park, Oak Kee Hong, Ji Won Kim, Bo Ryung Kim, Kun Ho Yoon
Korean Diabetes J. 2006;30(1):54-63.   Published online January 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.1.54
  • 1,659 View
  • 18 Download
AbstractAbstract PDF
BACKGROUND
Because of the shortage of human pancreas and immunorejection, very small fraction of patients with type 1 diabetes can be treated with islet transplantation. The immune tolerance induction for overcoming the immume rejectin of trausplamted islets could be conducted by hematopoietic mixed chimerims with various invasive methods. The purpose of this study is to investigate the effect of mixed chimerims conducted by newly developed minimally invasive methods on islet allografts rejection in streptozotocin induced diabetic mice. METHODS: Recipient, Balb/c(H-2Kd) mice were injected intraperitoneally with anti- asialoGM1 antibody at one day before bone marrow transplantation. There were received total body irradiation at a dose of 500 cGy and followed by tail vein injection of the 2 x 10(7) T-cell depleted bone marrow cells from C57BL/6(H-2Kb). Mixed chimerism mice were determined by gDNA PCR of lymphocyte MHC class I gene (H-2K) on 21st day. Streptozotocin induced diabetic mixed chimera mice were received islet transplantation from bone marrow donors. Grafts, spleen and peripheral blood were obtained from the mixed chimera mice, and there were used by Immunohistochimeical staining, flow cytometric analysis and gDNA PCR on 21st day. RESULTS: The blood glucose levels of streptozotocin induced diabetic mice were normalized by transplantation of bone marrow donor islets and maintained during 30 days. After removal of first islet allografts, hyperglycemia was re-established. We could re-confirmed donor specific tolerance of transplanted islets by second transplantation of bone marrow donor islets. Normoglycemia was maintained during 21 days after second islet transplantation. Furthermore islet grafts from MHC-mismatched third party mice were immediately rejected. Flow cytometric analysis results suggest that the mixed chimerism mice were maintain during the whole study period. CONCLUSION: The mixed chimerism model conducted by newly developed and minimally invasive method effectively prevents the islet allo grafts rejection in STZ-induced mixed chimerism mice.
Characterization of Preadipocyte factor-1 (Pref-1) Expressing Pancreatic Cells.
Marie Rhee, Sun Hee Suh, Youn Joo Yang, Ji Won Kim, Sung Yoon Jeon, Oak Kee Hong, Seung Hyun Ko, Yoon Hee Choi, Bong Yun Cha, Ho Yong Son, Kun Ho Yoon
Korean Diabetes J. 2005;29(6):507-516.   Published online November 1, 2005
  • 1,163 View
  • 22 Download
AbstractAbstract PDF
BACKGROUND
Preadipocyte factor-1/Delta-like 1(Pref-1/Dlk1) is a type I membrane protein that has six epidermal growth factor (EGF)-like repeats in its extracellular and a short cytoplasmic domain. It is widely expressed in embryonic tissues, whereas its expressions were limited in adult and postnatal stage. To characterize the Pref-1 expressing cells during pancreas development and regeneration after birth, we analyzed Pref-1 expression in embryonic and adult partial pancreatectomized rat pancreas, and primary cultured neonatal pig pancreatic cells. METHODS: Whole fetuses or pieces of rat pancreas were obtained at E20. 90% partial pancreatectomy (Px) and sham operation were done using 5 week-old Sprague-Dawley rats. Experimental animals were divided into 11 groups by time of killing after surgery; 0, 1, 3, 6 and 12 hours, 1, 2, 3, 5, 7, and 14 days. All tissues were immunostained with Pref-1 and analysed by reverse transcriptase (RT)-PCR. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. Cells were harvested on day 0, 3, 4, 5, 6, and 7 after dispersion. All cells were immunostained with Pref-1 and other specific cell markers such as Pan-cytokeratin (Pan-CK), vimentin (VT) and islet hormones, and confirmed by Western blot, RT-PCR and fluorescence activated cell sorting (FACS) analysis. RESULTS: In the rat embryonic pancreas at E20, Pref-1 expression was restricted only in the small branching ductules. In adult rat pancreas, Pref-1 was not expressed at all. Whereas, Pref-1 transiently expressed in the small regenerating duct cells located in foci of regeneration in Px model, then completely disappeared at day 7. The Pref-1 mRNA measured by RT-PCR was peaked at day 3 after Px and then gradually disappeared. Pref-1 expression pattern was also reproduced in monolayer cultured NPCCs. In NPCCs, protein levels of Pref-1 were peaked at day 0 to day 4 then gradually disappeared until day 7 by western blot. Most of Pref-1 expressing cells were co-stained with cytokeratin. The proportion of Pref-1 expressing cells in dispersed NPCCs were counted and isolated by FACS at 3 days after culture were 25% and then decreased over time during 7 days culture period. CONCLUSIONS: Pref-1 expression was regained in adult pancreatic cells during regeneration in vivo and in vitro and Pref-1 might be a useful marker for the pancreatic protodifferentiated cells.

Diabetes Metab J : Diabetes & Metabolism Journal