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Dong Sik Ham  (Ham DS) 3 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
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AbstractAbstract PDF
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
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AbstractAbstract PDF
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.
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
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  • 3 Crossref
AbstractAbstract PDF
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 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

Diabetes Metab J : Diabetes & Metabolism Journal