Fig. 7: Chronic GIPR agonism desensitizes GIPR activity in primary adipocytes. | Nature Communications

Fig. 7: Chronic GIPR agonism desensitizes GIPR activity in primary adipocytes.

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

Fig. 7: Chronic GIPR agonism desensitizes GIPR activity in primary adipocytes.

a cAMP measurements in primary differentiated mouse pre-adipocytes pre-treated with or without DA-GIP (1 μM) for 24 h then treated with vehicle, mouse GIP, or isoproterenol (1 μM) for 30 min; *p = 0.010, ****p ≤ 0.0001. b cAMP measurements in primary differentiated mouse pre-adipocytes pre-treated with or without DA-GIP (1 μM) for 24 h, washed, then treated with 100 nM mouse GIP for 30 min; ***p = 0.0003, ****p ≤ 0.0001. c cAMP measurements in primary differentiated mouse pre-adipocytes pre-treated with or without DA-GIP (1 μM) for 1, 4, or 24 h, then treated with 100 nM mouse GIP for 30 min; ****p ≤ 0.0001, ***p = 0.0003, 0/No GIP vs. 4 h/No GIP *p = 0.021, and 0/No GIP vs. 24 h/No GIP *p = 0.027. d cAMP measurements in primary differentiated mouse pre-adipocytes pre-treated with or without DA-GIP for 24 h, then treated with 100 nM mouse GIP for 30 min. ****p ≤ 0.0001. e FA uptake in primary differentiated mouse pre-adipocytes pre-treated with or without DA-GIP for 24 h, then treated with vehicle, mouse GIP, or insulin for 30 min. *p = 0.015, No DA-GIP Basal vs. No DA-GIP/Insulin **p = 0.0044, DA-GIP/Basal vs. DA-GIP/Insulin **p = 0.0022. f cAMP measurements in primary human adipocytes differentiated in vitro pre-treated with or without DA-GIP for 24 h then treated with vehicle, human GIP, or isoproterenol for 30 min. *p = 0.011, ***p = 0.0009, 100 nM GIP/No DA-GIP vs. 100 nM GIP DA-GIP **p = 0.0065, and Basal/DA-GIP vs. Isoproterenol/DA-GIP **p = 0.0011. a–f Data represent means ± SEM of four mice with three wells/treatment/mouse (a–d), three mice with three wells/treatment/mouse (e), three human donors with three wells/treatment/person (f); two-way repeated measures ANOVA with Sidak’s multiple comparisons test. g Mouse Neuro-2a neuroblastoma cells and h rat INS1 832/13 islet cells pre-treated with mouse or rat GIP (1 μM), respectively, for 24 h then treated with mouse or rat GIP in a dose response for 15 min; n = 2 wells/treatment.

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