The regulation of the induction of vascular endothelial growth factor at the onset of diabetes in spontaneously diabetic rats.

Early induction of VEGF was studied in liver, kidney and lung of spontaneously diabetic rats. Western blot analysis, northern hybridization were applied to show the expression of VEGF in different organs. Radiolabelled hypoxia responsive element (HRE) and cAMP responsive element (CRE) oligonucleotides were assayed by electrophoretic mobility shift (EMSA) or supershift using anti ARNT and anti CREB-1 monoclonal antibodies. An increase in VEGF expression at the level of protein and mRNA was demonstrated at the beginning of the disease. EMSAs showed: a.) a binding of HIF-1 to HRE and/or CRE, b.) in the same time the binding of CREB- I was detected to both HRE and/or CRE sequences in the liver, kidney and lung of diabetic animals. Based on these in vivo observations it is supposed that HRE and CRE through the interaction between HIF-1 and CREB-1 are equally involved in the regulation of VEGF expression at the onset of diabetes.