Fig. 3. β-Cells lacking Insr have increased action potential and calcium oscillation frequencies.

a Representative traces of action potential firing in β-cells from 16 week-old chow-fed female mice (n = 16–17 cells, from three mice per group). Glucose changed as indicated. b, c Quantification of action potential (AP) properties (Hz, mV) and reversal potential (mV) during the 10 mM glucose phase in patch clamped dispersed female β-cells (n = 16–17 cells, from three mice per group). Unpaired two-sided student’s t-test. d Quantification of electrophysiological properties in islets from male mice (n = 9–10 cells, from three mice per group). Unpaired two-sided student’s t-test. e, f β-Cell exocytosis measured as increased membrane capacitance normalized to initial cell size (fF/pF) over a series of ten 500 ms membrane depolarizations from −70 to 0 mV (n = control 32 cells, 29 βInsr^KO cells, from three pairs of mice). Unpaired two-sided student’s t-test. g Ca²⁺ dynamics measured in dispersed islet cells (Fura-2 340/380 ratio) treated as indicated from a baseline of 3 mM glucose) (n = 3523 cells, 3–5 image areas per experiment, 1–2 independent islet cultures from six LFD-fed female 12-week old mice, two mice from each group). h Quantification of glucose induced Ca²⁺ oscillation number (n = see g). ANOVA with correction for multiple comparisons using Tukey’s method. Additional quantification of these traces can be found in Fig. S2A. Boxplot; Minima: minimum outliers; Maxima: maximum outliers; Center: median; Bounds of box: first to third quartile; Whiskers: the upper whisker extends from the hinge to the largest value no further than 1.5 * IQR from the hinge (where IQR is the inter-quartile range, or distance between the first and third quartiles). The lower whisker extends from the hinge to the smallest value at most 1.5 * IQR of the hinge. i, j Oxygen consumption rate (OCR) data ((pmol/min) normalized to ug protein with non metabolic rate (non-MR) subtracted) of independent dispersed islet cultures from 16 week-old chow-fed control, βInsr^HET, and βInsr^KO mice (three male and one female mice from each group). Data were analyzed with a fitted mixed-effects model with correction for multiple comparisons using Dunnett’s method. βInsr^WT (black bars), βInsr^HET (female = light pink bars, male = light blue bars) and βInsr^KO (female = dark red bars, male = dark blue bars). All samples were handled in a strictly blinded manner. All data are presented as mean values +/− SEM. Source data are provided as Source Data file.