To examine whether a cause-and-effect relationship exists between the overexpression of CREM/ICER in diabetic SIECs, the aberration in angiogenic capacity and PKA-CREB-dependent signaling, we downregulated the diabetes-mediated increase in CREM/ICER level using an siRNA-based strategy; transfection efficiency was confirmed by using real-time PCR and western blotting. The gene discussed is CREB1; the disease is diabetes mellitus.