INS and diabetes mellitus: Besides, studies have demonstrated that insulin maintained the perfusion of microvasculature in a nitric oxide (NO)–dependent manner [40], enhanced the expression of VE-cadherin and β-catenin in human fetoplacental vessels from pregnancies with diabetes [41], protected endothelial barrier function by suppressing endothelial contractile machinery and strengthening cell-cell adhesions through PI3K/Akt- and NO/cGMP-induced Rac1 activation [42].