Fig. 2: Metabolic phenotype of HFD-fed male Per-Gipr KO mice.
a, Body weight development of male C57BL6/J Per-Cre+Giprwt/wt (WT) and Per-Cre+Giprflx/flx (KO) mice fed with a HFD (n = 8 each group). b,c, Fat (b) and lean (c) tissue mass of 44-week-old male WT and KO mice (n = 8 each group). d, Cumulative food intake of male WT and KO mice, measured per cage in double-housed mice from age 14 to 47 weeks (n = 8 each group). e–g, Energy expenditure (e), locomotor activity (f) and RER (g) of 49-week old male WT and KO mice (n = 8 each group). h,i, HbA1c in 46-week-old male WT and KO mice (n = 8 each group) (h), as well as glucose tolerance (i) after i.p. dosing with 1.5 g kg−1 glucose in 47-week-old male WT and KO mice (n = 7 each group). j, Insulin tolerance after i.p. dosing with 1.5 U kg−1 insulin (Humalog) in 48-week-old male WT and KO mice (n = 8 each group). k,l, Glucose-induced insulin secretion (n = 7 WT and n = 8 KO) (k) and corresponding levels of total GIP (n = 8 WT and n = 6 KO) (l) after oral glucose bolus administration of 4 g kg−1 glucose in 51-week-old male WT and KO mice. m, Insulin secretion, expressed as fold difference between high and low glucose (2.68 mM and 20 mM) in isolated islets from 46-week-old chow-fed male WT and KO mice treated with either vehicle or 50 nM of either native mouse GIP or GLP-1 (n = 12 independent biological samples per group). n–p, Fasting levels of blood glucose (n) and insulin (o) in 51-week-old male WT and KO mice (n = 8 each group), as well as triglycerides (p) in 52-week-old male WT (n = 7) and KO mice (n = 8). Data in a, d and i–k were analysed by two-way ANOVA with Bonferroni’s post hoc test for comparison of individual timepoints. Data in b, c, h, i and n–p were analysed using two-sided, two-tailed Student’s t-test. Data in f and g were analysed using a two-tailed, unpaired Mann–Whitney test. Data in m were analysed using a one-way ANOVA. Data in e were analysed using ANCOVA with body weight as the covariate. Cumulative food intake (d) was assessed per cage in n = 8 double-housed mice in each group. For data in m, handpicked islets of similar size were distributed per animal to achieve one well per treatment group (three wells per animal), each containing ten islets per well. Data represent mean ± s.e.m. *P < 0.05, **P < 0.01 and ***P < 0.001. Individual P values are shown in the Source data, unless P < 0.0001.
