We therefore conclude that varying degrees of genetic suppression of KATP channel activity will all lead to enhanced excitability, but with different long-term consequences for insulin secretion, depending on the severity of suppression: incomplete loss of KATP channels (e.g., in Kir6.2[AAA] [13] or in heterozygous Kir6.2+/− or SUR1+/− mice [14]) causes a maintained hyperinsulinism, whereas complete loss (in Kir6.2- and SUR1-KO mice) causes transient hypersecretion that is followed by a secretory deficit and reduced glucose tolerance [10–12]. Here, INS is linked to hyperinsulinism.