RT Journal Article
SR Electronic
T1 Pancreatic Islet Production of Vascular Endothelial Growth Factor-A Is Essential for Islet Vascularization, Revascularization, and Function
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 2974
OP 2985
DO 10.2337/db06-0690
VO 55
IS 11
A1 Brissova, Marcela
A1 Shostak, Alena
A1 Shiota, Masakazu
A1 Wiebe, Peter O.
A1 Poffenberger, Greg
A1 Kantz, Jeannelle
A1 Chen, Zhongyi
A1 Carr, Chad
A1 Jerome, W. Gray
A1 Chen, Jin
A1 Baldwin, H. Scott
A1 Nicholson, Wendell
A1 Bader, David M.
A1 Jetton, Thomas
A1 Gannon, Maureen
A1 Powers, Alvin C.
YR 2006
UL http://diabetes.diabetesjournals.org/content/55/11/2974.abstract
AB To investigate molecular mechanisms controlling islet vascularization and revascularization after transplantation, we examined pancreatic expression of three families of angiogenic factors and their receptors in differentiating endocrine cells and adult islets. Using intravital lectin labeling, we demonstrated that development of islet microvasculature and establishment of islet blood flow occur concomitantly with islet morphogenesis. Our genetic data indicate that vascular endothelial growth factor (VEGF)-A is a major regulator of islet vascularization and revascularization of transplanted islets. In spite of normal pancreatic insulin content and β-cell mass, mice with β-cell–reduced VEGF-A expression had impaired glucose-stimulated insulin secretion. By vascular or diffusion delivery of β-cell secretagogues to islets, we showed that reduced insulin output is not a result of β-cell dysfunction but rather caused by vascular alterations in islets. Taken together, our data indicate that the microvasculature plays an integral role in islet function. Factors modulating VEGF-A expression may influence islet vascularity and, consequently, the amount of insulin delivered into the systemic circulation.