In conclusion, here we demonstrate that arterial TMEM16A transcription is regulated by a Snail-mediated repressor complex and that high glucose and insulin resistance activate protein kinase D1 and GSK3β, respectively, to induce phosphorylation and degradation of Snail to increase TMEM16A expression in arterial smooth muscle and cause vasoconstriction. The gene discussed is PRKD1; the disease is Insulin resistance.