VSG restores glycaemia and improves β-cell function in overtly diabetic db/db mice. A, Schematic of single-cell experiment. 16- to 18-week-old db/db mice were subjected to VSG, sham surgery (Sham) and sham surgery with subsequent pair-feeding. Animals were challenged with a mixed-meal tolerance test (MMTT) two weeks prior to surgery and one day before the end of experiment at day 14, followed by islet scRNA-seq (age 18–20 weeks). B, Postsurgical changes in BW (WT, n = 8; Sham, n = 6, PF, n = 6; VSG, n = 4; two-way ANOVA with Bonferroni's post hoc test; differences in VSG versus Sham and VSG versus PF were not statistically significant; VSG versus WT (d4, p = 0.099; d5, p = 0.0045; d6-d14, p < 0.0001)). C, Fasting blood glucose (WT, n = 7; Sham, n = 7, PF, n = 5; VSG, n = 4; one-way ANOVA with Bonferroni's post hoc test; WT versus Sham (p < 0.0001), WT versus PF (p < 0.0001), Sham versus VSG (p < 0.0001), PF versus VSG (p = 0.0003)) and D, fasting insulin levels (WT, n = 8; Sham, n = 6; PF, n = 4; VSG, n = 4; one-way ANOVA with Bonferroni's post hoc test; WT versus VSG (p < 0.0001), Sham versus VSG (p = 0.0008), PF versus VSG (p = 0.0047)). E, Area under the curve (AUC) of blood glucose levels during an MMTT (WT, n = 7; Sham, n = 7, PF, n = 5; VSG, n = 4; one-way ANOVA with Bonferroni's post hoc test; Sham versus VSG (p < 0.0001); PF versus VSG (p = 0.0011) F, AUC of insulin levels during an MMTT (WT, n = 8; Sham, n = 7, PF, n = 5; VSG, n = 4; one-way ANOVA with Bonferroni's post hoc test; Sham versus VSG (p = 0.0002); PF versus VSG (p = 0.0016). All data are presented as mean ± s.e.m.