Fig. 1: Whole-body inceptor deletion improves glucose metabolism in male mice with DIO.

a, Inceptor immunoreactivity in whole brain, pituitary and pancreas of 10-week-old male C57BL/6J inceptor Iir+/+ (WT) and Iir−/− (KO) mice. Scale bars, 1 mm for brain, 200 µm for pituitary and 20 µm for pancreas. b,c, Food intake (b) in 28-week-old and body weight (c) in 10- to 30-week-old male C57BL/6J WT and KO mice (n = 8 for each genotype). d,e, Intraperitoneal glucose tolerance (d) and area under the curve (AUC) (e) in 19-week-old male C57BL/6J WT and KO mice (n = 7 WT, n = 8 KO). f,g, Intraperitoneal insulin tolerance (f) and AUC (g) in 23-week-old male C57BL/6J WT and KO mice (n = 8 for each genotype). h,i, Fasting levels of plasma insulin (n = 8 for each genotype) in 19-week-old male C57BL/6J WT and KO mice (n = 8 for each genotype) (h) and levels of HbA1c in 27-week-old male C57BL/6J WT and KO mice (n = 8 for each genotype) (i). j, Glucose-stimulated insulin secretion in 27-week-old male C57BL/6J WT and KO mice (n = 8 for each genotype). k,l, Western blots of liver protein of 30-week-old male C57BL/6J WT and KO mice treated with a single dose of saline or 1 mU per kg of insulin (n = 4 for each group) (k) and densitometric quantification (l). m,n, Pancreatic α cell (m) and β cell (n) mass in 30-week-old male C57BL/6J WT and KO mice (n = 5 for each genotype). o,p, Fasting plasma levels of glucagon (o) and blood glucose (p) in 19-week-old male C57BL/6J WT and KO mice (n = 8 for each genotype). *P < 0.05, **P < 0.01, ***P < 0.001. Data are presented as mean ± s.e.m. Data in b, e, g–i and l–p were analysed by two-sided, two-tailed Student’s t-test. Data in c, d, f and j were analysed by two-way ANOVA with Bonferroni’s post hoc, multiple-comparison test for the different time points. P values for group differences are: P = 0.0049 (c), P = 0.0082 (d), P = 0.010 (e), P = 0.0098 (i), P = 0.0021 (j), P = 0.002 (WT) and P = 0.0016 (KO) (l) and P = 0.0232 (o). P values for the multiple-comparison tests are provided in Source data. Corr., corrected; vhcl, vehicle.