Allan Langlois
Strasbourg University, France
Title: Impact of hyperglycemia on islets revascularization deficiency post intraportale transplantation
Biography
Biography: Allan Langlois
Abstract
Vascular Endothelial Growth Factor (VEGF)–VEGF receptor 2 (VEGFR2) signaling pathway is the key regulator of islet revascularization post graft. However, in diabetics, studies suggest that this axis activation is impaired in tissues like the lung, due to a decrease of VEGFR2 expression. The aim of this work was to compare VEGFR2 expression in the liver between diabetic and control rats and to understand the impact of hyperglycemia on its expression.
The study was realized on healthy and diabetic Wistar rats induced by intraperitoneal injection of streptozotocine (100mg/kg). Diabetic rats were treated or not with Insuplant® administered using a subcutaneous osmotic-pump (2UI/day). After 6 weeks, rats were sacrificed, plasma and livers recovered. VEFGR2 expression was measured by western blotting, glycaemia using glucometer, c-peptide by ELISA kit and oxidative stress (OS) using DHE staining.
VEGFR2 expression is reduced in the liver of untreated diabetic rats (0.09±0.02 vs control: 0.40±0.03 VEGFR2/β-actin protein expression; p<0.001). Moreover, insulin improved this expression (diabetics+insulin: 0.22±0.06 VEGFR2/β-actin protein expression; p<0.05) but to a lower level than control. Then, OS is increased in untreated diabetics (141.5±8.7% of staining vs control; p<0.05). With insulin, OS returned to control level and was less important than diabetic untreated rats (p=0.07 vs untreated diabetics).
As the liver is the principal site of islet transplantation, VEFGR2 underexpression could explain the delay of graft revascularization. Moreover, hyperglycemia inducing OS could be responsible of the decreasing of VEGFR2 expression. Finally, we have to confirm this role and to develop anti-oxidative strategies to stimulate VEGFR2 expression.