Fig. 1: Generation of a long-acting GIPR agonist (LA-Agonist) for chronic in vivo studies. | Nature Communications

Fig. 1: Generation of a long-acting GIPR agonist (LA-Agonist) for chronic in vivo studies.

From: Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism

Fig. 1: Generation of a long-acting GIPR agonist (LA-Agonist) for chronic in vivo studies.

a GIPR agonist activity of LA-Agonist and mouse GIP in cells overexpressing mouse GIPR determined by measuring cAMP. n = 2 wells/treatment. b, c Pharmacodynamic (PD) assay for LA-Agonist-stimulated insulin secretion. DIO mice were injected with saline or LA-Agonist, fasted for 4 h, injected with glucose and saline or glucose and DA-GIP as indicated. b Blood glucose and c plasma insulin were measured over time. n = 8 mice/group; two-way repeated measures ANOVA with Dunnett’s multiple comparisons test, **p = 0.0048 and ****p ≤ 0.0001 vs. vehicle/saline. Data are presented as mean values ± SEM. d, e LA-Agonist exposure from samples taken at 4-h post dose of LA-Agonist in the same PD assay presented in b, c were correlated to individual response for d glucose and e insulin, based on 0–60 min AUC calculated from b and c, respectively. n = 8 mice/treatment. Data are presented as mean values ± SEM. f Single-dose pharmacokinetic (PK) study of LA-Agonist was evaluated in CD-1 mice both by intravenous (IV) and intaperitoneal (IP) injections. Plasma was collected over time and used to measure intact LA-Agonist. n = 3 mice/timepoint. Data are presented as mean values ± SEM.

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