K_ATP channels in pancreatic β cells act as the systemic glucostat. (A) 3-stage monitoring of blood glucose levels. Ad libitum: P < 0.0001, F (5, 44) = 14.23; fasting: P = 0.0204, F (5, 44) = 3.003; re-feeding: P = 0.0001, F (5, 44) = 6.492; made by two-way ANOVA with Tukey’s correction. (B) The average blood glucose levels during ad libitum. (C) The fluctuation range of blood glucose levels during ad libitum, which is derived from the difference between the maximum and minimum value of individual mouse ad libitum blood glucose levels. (D) Plasma insulin concentration in mice after a 24-hour fasting duration and 30 minutes after re-feeding. WT: n = 6 (A-C), 3 (D); Kir6.2 KO: n = 6 (A–C), 4 (D); Ins1^Cre/0; Kir6.2^flox/+: n = 6 (A-C), 3 (D); Ins1^Cre/0; Kir6.2^flox/flox: n = 14 (A-C), 4 (D); Nestin^Cre/0; Kir6.2^flox/+: n = 11 (A-C), 3 (D); Nestin^Cre/0; Kir6.2^flox/flox: n = 7 (A-C), 3 (D). Statistical comparisons were made by two-way ANOVA with Tukey’s correction followed by multiple comparisons (A) or Šídák’s correction followed by multiple comparisons (B-D). Data are represented as mean ± SEM. *P < 0.05, **P < 0.01, ****P < 0.0001, ns: not significant.