Liprin-α1 knockdown in mouse β cells reduces both phases of glucose-stimulated insulin secretion. (A) Static incubation of β cells infected with adenovirus encoding GFP-scrambled shRNA (control) or GFP–liprin-α1 shRNA in 16.7 mM glucose for 30 min showed a significant reduction in insulin secretion, normalized to total cellular insulin content, after liprin-α1 knockdown. Re-expression of GFP-human–liprin-α1 rescued this secretory defect (for each condition, n = 3 animals; two-way ANOVA followed by Tukey’s multiple comparisons test). (B–E) Dynamic glucose-stimulated insulin secretion profiles from perifused β cells. Insulin secretion in both first phase (10 min following stimulation) and second phase (20–40 min following stimulation) was reduced after liprin-α1 knockdown, quantified by measuring area under curve (AUC). (F and G) β cells were loaded with Fura-2 to measure intracellular [Ca²⁺]. In both liprin-α1 knockdown and control groups, robust Ca²⁺ responses were recorded following stimulation with 16.7 mM glucose with no difference in area under curve (n ≥ 9 β cell clusters from 3 animals; Student’s t test, unpaired, equal variance.