| First Author | De Leu N | Year | 2014 |
| Journal | Diabetologia | Volume | 57 |
| Issue | 1 | Pages | 140-7 |
| PubMed ID | 24121626 | Mgi Jnum | J:206478 |
| Mgi Id | MGI:5550330 | Doi | 10.1007/s00125-013-3076-9 |
| Citation | De Leu N, et al. (2014) Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes. Diabetologia 57(1):140-7 |
| abstractText | AIMS/HYPOTHESIS: Vascular endothelial growth factor (VEGF) has been recognised by loss-of-function experiments as a pleiotropic factor with importance in embryonic pancreas development and postnatal beta cell function. Chronic, nonconditional overexpression of VEGF-A has a deleterious effect on beta cell development and function. We report, for the first time, a conditional gain-of-function study to evaluate the effect of transient VEGF-A overexpression by adult pancreatic beta cells on islet vasculature and beta cell proliferation and survival, under both normal physiological and injury conditions. METHODS: In a transgenicmouse strain, overexpressing VEGF-A in a doxycycline-inducible and beta cell-specific manner, we evaluated the ability of VEGF-A to affect islet vessel density, beta cell proliferation and protection of the adult beta cell mass from toxin-induced injury. RESULTS: Short-term VEGF-A overexpression resulted in islet hypervascularisation, increased beta cell proliferation and protection from toxin-mediated beta cell death, and thereby prevented the development of hyperglycaemia. Extended overexpression of VEGF-A led to impaired glucose tolerance, elevated fasting glycaemia and a decreased beta cell mass. CONCLUSIONS/INTERPRETATION: Overexpression of VEGF-A in beta cells time-dependently affects glycometabolic control and beta cell protection and proliferation. These data nourish further studies to examine the role of controlled VEGF delivery in (pre)clinical applications aimed at protecting and/or restoring the injured beta cell mass. |
