INS and hyperinsulinism: We therefore propose that varying degrees of genetic suppression of KATP channels will all lead to enhanced excitability and insulin secretion, but with potentially very different long-term consequences depending on the severity of suppression: incomplete loss of KATP channels (e.g., in Kir6.2[AAA] or in heterozygous Kir6.2+/− or SUR1+/− mice) causes a persistent hyperinsulinism, whereas complete loss (e.g., in KATP KO mice) may transiently cause hypersecretion, but this is followed by a secretory deficit and reduced glucose tolerance (Figure 7C) [14,42].