PCK2 and hyperinsulinemic hypoglycemia, familial, 4: When inducing insulin insufficiency in a Gcgr-/- background, a situation of combined insulin and glucagon deficiency, we observed Pepck and Gck mRNA levels similar to those measured in untreated Gcgr+/- control mice, except after DT, which induced a strong downregulation of Gck expression in Gcgr-/- livers (Figure 4D).