Quantification of the whole cell mass in NOD mice administered daily with either saline or 0.4 or 0.8 mg/kg of native RSPO1. The cell mass of 10-week-old NOD females was used to evaluate the insulin+area at the beginning of the study (n= 15 in control group,n= 10 to 13 in treated groups). All data shown represent mean SEM. Results were considered significant ifp< 0.0001 (****),p< 0.001 (***),p< 0.01 (**), andp< 0.05 (*) following a two-way ANOVA (A–D); an unpaired Student’s t test or Mann-Whitney test (B), a mixed-effect model (restricted maximum likelihood, REML) with a Dunnett’s comparison test (C); and a one-way ANOVA, a Mann-Whitney test, or a Kruskal-Wallis test (E). See alsoFigures S4andS5.