Effect of Vps13c deletion on GSIS in vitro. A–D: insulin secretion from isolated islets from KO and Ctrl mice over 20 wk old maintained on RC (A and C) or HFD (B and D) was assessed by incubating 10 size-matched islets in Krebs-Ringer solution containing 3 mM glucose (3 Glu), 16.7 mM glucose (16.7 Glu), or 20 mM KCl for 30 min and measuring the amount of insulin secreted (see materials and methods). Islets were lysed to measure total insulin; results are presented as %total insulin. E: insulin secretion from islets continuously perifused with Krebs-Ringer solution containing 3 mM glucose and then stimulated with 16.7 mM glucose; n = 3–5 mice per genotype, as indicated. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, 2-way ANOVA with Sidak or Tukey's post hoc test where appropriate.