Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus

Autor: Ki Ho Song, Seung Hyun Ko, Ji-Won Kim, Myung-Jun Kim, In Kyung Jeong, Kun Ho Yoon, Heon Seok Park, Dong Sik Ham, Yu Bai Ahn, Ki Dong Yoo
Rok vydání: 2009
Předmět:
Zdroj: Korean Diabetes Journal. 33:185
ISSN: 1976-9180
Popis: Background: Vascular endothelial growth fact or (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF tre atment 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 ant agonist) 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. T he 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. (Korean Diabetes J 33:185-197, 2009)
Databáze: OpenAIRE