Fig. 8

Antidiabetic effects of exendin-phe1 in vivo. a Blood glucose during IPGTT (2 mg kg⁻¹ glucose) performed in HFHS mice at the indicated time-points after intraperitoneal (IP) injection of agonist (2.4 nmol kg⁻¹), n = 10/group except vehicle group at 4/8 h (n = 9), two-way repeat measures ANOVA with Tukey’s test, with significance vs. exendin-4 shown. b AUC determined from a, relative to baseline glucose at t = 0, the two-way ANOVA with Dunnett’s test vs. 0 h. c Plasma insulin before and 10 min after IP administration of glucose (2 g kg⁻¹) in HFHS mice, at indicated time-point after IP injection of agonist (2.4 nmol kg⁻¹), n = 10/group except vehicle 0 h (n = 8) and 4 h vehicle/exendin-4 (n = 9), two-way repeat measures ANOVA with Sidak’s test. d Plasma drug level at indicated time-points after IP injection of agonist (24 nmol kg⁻¹), n = 4 per group, two-way repeat measures ANOVA with Sidak’s test. e Cumulative food intake in fasted HFHS mice after IP injection of agonist (2.4 nmol kg⁻¹), n = 8/group. f Observed pica behavior in fasted lean mice treated with IP agonist (2.4 nmol kg⁻¹), n = 8/group, Mann–Whitney test comparing exendin-4 vs. exendin-phe1. g Relationship between agonist-induced GLP-1R internalization efficacy (Supplementary Fig. 1) and glucose lowering during IPGTT (Supplementary Fig. 10g), assessed as AUC relative to glucose at t = 0, relationship quantified by linear regression. *p < 0.05, **p < 0.01, ***p < 0.001, by statistical test indicated above. Error bars indicate SEM