Generation of VPS13Cfl/fl::Ins1.Cre+/− (βVps13cKO) mice. A: LoxP sites were inserted on either side of exon 1 to enable Cre-mediated inactivation of the Vps13c gene in pancreatic β-cells after breeding to Ins1.Cre mice. The resultant colony consisted of VPS13C-null mice (KO, βVps13cKO) and control mice (Ctrl) at the expected 50:50 ratio. B and C: islets were isolated from 2–3 male (B) and 3 female (C) Ctrl and KO mice for (i) immunoblotting or (ii) qPCR analysis. Both ΔCT (relative to cyclophilin A) and log2-transformed fold changes, normalized to control mice, are shown. Error bars represent standard deviation in (ii) top and 95% confidence intervals in (ii) bottom. *P < 0.05, **P < 0.01 analyzed with 2-way ANOVA with Sidak's multiple corrections. D–G: changes in weight (D and E) and random-fed glycemia (F and G) over time for Ctrl (black) and KO (dashed) mice fed regular chow (RC, circles or squares) or high-fat diet (HFD, triangles). Inset: area under the curve (AUC) analysis for female mice on HFD, assessed for significance using an unpaired Student's t-test; n = 11–15 mice, as indicated.