INS and Hyperinsulinemia: Circulating ET-1 concentrations rapidly elevate with hyperinsulinemia (Wolpert et al. 1993; Ferri et al. 1995) though there is a paucity of evidence for ET-1 signaling, in vivo, beyond 2 h post insulin stimulation and human prepro-ET-1 mRNA is labile with an intracellular half-life of ∼15 min (Inoue et al. 1989).