In two papers in the journal Diabetes and one each in Development and Cell Metabolism, the researchers described four main findings about islet vascularization and innervation:
First, vascular endothelial growth factor A (VEGF-A) is important for development of the islets' blood supply and for beta-cell proliferation. Blocking the growth factor early in development in a mouse model ultimately reduced beta-cell mass and insulin release and impaired glucose clearance from the bloodstream.
Other Vanderbilt scientists involved in this work were postdoctoral fellow Fong Cheng Pan, Ph.D., and Owen McGuinness, Ph.D., professor of Molecular Physiology and Biophysics.
Second, VEGF and other "signals" released by the endothelial cells lining islet blood vessels consequently stimulated growth of islet nerves in mice that connected to the brain.
"If the islets don't become vascularized properly, they don't become innervated properly," Brissova said. These signals also promote beta cell growth.
Other Vanderbilt scientists involved in this research were Ambra Pozzi, Ph.D., professor of Medicine, and Christopher V.E. Wright, D.Phil., Louise B. McGavock Professor, Department of Cell and Developmental Biology.
Third, VEGF-A was not involved when the beta-cell mass increased in an obese mouse model of type 2 diabetes in response to rising glucose levels.
Unlike tumors, which sprout new blood vessels as they grow, the beta-cell tissue increased its blood supply by dilating existing vessels.
Other Vanderbilt scientists involved in this research were Takamune Takahashi, M.D., Ph.D., associate professor of Medicine; Masakazu Shiota, DVM, Ph.D., associate professor of Molecular Physiology and Biophysics; and Eric H. Liu, M.D., assistant professor of Surgery.
Finally, too much VEGF-A can lead to beta cell death. But that sets up a regenerative microenvironment involving an in
|Contact: Craig Boerner|
Vanderbilt University Medical Center