Figure 1. Specific deletion of the Kcnj11 gene in β cells (βKcnj11^–/–) severely impairs glucose tolerance and GIIS in mice.

(A) Electrophysiology of β cells of Kcnj11^fl/fl and βKcnj11^–/– mice. Left: representative recordings of whole-cell K_ATP currents in primary β cells isolated from Kcnj11^fl/fl and βKcnj11^–/– mice. Middle: conductance normalized to cell capacitance (n = 14 for Kcnj11^fl/fl; n = 16 for Kcnj11^fl/fl mice). Right: resting membrane potential of primary β cells from control and βKcnj11^–/– mice measured by perforated patch (n = 7). (B) oGTT and corresponding plasma insulin levels. Left: blood glucose (n = 12). Right: plasma insulin (n = 17–20 for each point). (C) Plasma levels of total incretins in Kcnj11^fl/fl and βKcnj11^–/– mice. Glucose (1.5 g/kg) was administered to conscious mice fasted for 6 hours (n = 9–14 for each point). (D) Insulin secretion from perfused mouse pancreases. Mice were fasted overnight before perfusion experiments commenced (n = 4). (E) Dose-dependent effects of glucose on insulin secretion from the islets of Kcnj11^fl/fl and βKcnj11^–/– mice. Islets were preincubated for 30 minutes in KRBΒ containing 2.8 mM glucose and then stimulated with concentrations of glucose as indicated (0.5, 2.8, 5.6, 8.8, 11.1, and 16.7 mM) for 30 minutes (n = 6-8 for each point). A representative result of 3 independent experiments is shown. Statistical analyses were performed by 2-tailed Student’s unpaired t test (A) or 2-way ANOVA by followed by Dunnett’s post hoc test (B–E). Data are represented as mean ± SEM. *P < 0.05; **P < 0.01.