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DOI: 10.1055/s-2008-1081486
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Reduced Insulin Secretion and Content in VEGF-A Deficient Mouse Pancreatic Islets
Publication History
received 18.02.2008
accepted 20.03.2008
Publication Date:
05 September 2008 (online)
Abstract
Mice, deficient for vascular endothelial growth factor VEGF-A in pancreatic islets, have reduced insulin gene expression levels and an impaired glucose tolerance. Here, we investigated whether VEGF-A was required for physiological glucose-stimulated insulin secretion and insulin content. We performed in situ pancreas perfusions and islet perifusions on mice lacking VEGF-A in the pancreatic epithelium in order to study their ability to secrete insulin in response to glucose. We identified insulin secretion defects in the pancreata of VEGF-A deficient mice, including a delayed and blunted response to glucose. Islet perifusion experiments revealed a missing first phase and weaker second phase of insulin secretion, in two of three VEGF-A deficient mice. On average, insulin content in VEGF-A deficient islets was significantly reduced when compared with control islets. We conclude that VEGF-A is required in pancreatic islets for normal glucose-stimulated insulin secretion and physiological insulin content. Thus, VEGF-A is a key factor for pancreatic islet function.
Key words
vascular endothelial growth factor - capillary network - pancreatic islet - insulin secretion - pancreas perfusion - islet perifusion
References
- 1 Kamba T, Tam BY, Hashizume H. et al . VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006; 290 H560-H576
- 2 Inoue M, Hager JH, Ferrara N, Gerber HP, Hanahan D. VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic beta cell carcinogenesis. Cancer Cell. 2002; 1 193-202
- 3 Lammert E, Gu G, MacLaughlin M. et al . Role of VEGF-A in vascularization of pancreatic islets. Curr Biol. 2003; 13 1070-1074
- 4 Zhang N, Richter A, Suriawinata J. et al . Elevated vascular endothelial growth factor production in islets improves islet graft vascularization. Diabetes. 2004; 53 963-970
- 5 Lai Y, Schneider D, Kidszun A. et al . Vascular endothelial growth factor increases functional beta-cell mass by improvement of angiogenesis of isolated human and murine pancreatic islets. Transplantation. 2005; 79 1530-1536
- 6 Gorogawa S, Fujitani Y, Kaneto H. et al . Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice. Biochem Biophys Res Commun. 2004; 319 1159-1170
- 7 Nikolova G, Jabs N, Konstantinova I. et al . The vascular basement membrane: a niche for insulin gene expression and beta cell proliferation. Dev Cell. 2006; 10 397-405
- 8 Knoch KP, Bergert H, Borgonovo B. et al . Polypyrimidine tract-binding protein promotes insulin secretory granule biogenesis. Nat Cell Biol. 2004; 6 207-214
- 9 Maechler P, Gjinovci A, Wollheim CB. Implication of glutamate in the kinetics of insulin secretion in rat and mouse perfused pancreas. Diabetes. 2002; 51 ((Suppl 1)) S99-S102
- 10 Brenner MB, Mest HJ. A buffer temperature controlled perifusion system to study temperature dependence and kinetics of insulin secretion in MIN6 pseudoislets. J Pharmacol Toxicol Methods. 2004; 50 53-57
Correspondence
E. Lammert
Max Planck Institute of Molecular Cell Biology and Genetics
Pfotenhauerstr. 108
01307 Dresden
Germany
Phone: +49/351/210 27 77
Fax: +49/351/210 12 09
Email: lammert@mpi-cbg.de