Here, we show that perinatal (postnatal days P1–P3) of later (P28–P32) inhibition of endothelial PKA using dominant-negative PKA expressed under the control of endothelial-specific Cdh5-CreERT2 recombinase (dnPKAiEC mice) leads to severe subcutaneous edema, hypoalbuminemia, hypoglycemia and premature death. Here, CDH5 is linked to Hypoglycemia.