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Original Article 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
Diabetes & Metabolism Journal 2009;33(3):185-197
DOI: https://doi.org/10.4093/kdj.2009.33.3.185
Published online: June 1, 2009
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1Division of Endocrinology & Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea. kosh@catholic.ac.kr
2Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
3Department of Physiology, The Catholic University of Korea, Seoul, Korea.
4Division of Endocrinology & Metabolism, Department of Internal Medicine, Kyung-Hee Uiversity, Seoul, Korea.
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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.

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    Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus.
    Korean Diabetes J. 2009;33(3):185-197.   Published online June 1, 2009
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Kim JW, Ham DS, Park HS, Ahn YB, Song KH, Yoon KH, Yoo KD, Kim MJ, Jeong IK, Ko SH. Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus.. Diabetes Metab J. 2009;33(3):185-197.
DOI: https://doi.org/10.4093/kdj.2009.33.3.185.

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