Figure 4.

Elimination of β cell-derived DPP4 does not improve glucose tolerance, incretin levels, or GSIS in HFD-fed female mice

(A–C) Oral glucose tolerance (A), active GIP (B), and insulin secreted (C) in female HFD-fed Dpp4^{β-cell−/−} and MIP-Cre control mice in response to oral glucose gavage ± sitagliptin.

(D–F) Intraperitoneal (i.p.) glucose tolerance (D), active GIP (E), and insulin secreted (F) in female HFD-fed Dpp4^{β-cell−/−} and MIP-Cre control mice in response to i.p. glucose injection. Sitagliptin was given by oral gavage 30 min prior to glucose tolerance tests (2 g/kg body weight for oGTT and at 1.2 g/kg for ipGTT) (n = 7–10 per group).

(G) Glucose levels and AUC during an insulin (0.6 IU/kg) tolerance test in female HFD-fed Dpp4^{β-cell−/−} and MIP-Cre control mice.

(H) Insulin tolerance test glycemia as a percentage of fasted glucose and AUC.

(I) GSIS measured during perifusion of islets isolated from 65-week-old HFD-fed Dpp4^{β-cell−/−} (n = 4) and MIP-Cre control (n = 4) mice with arginine (1 mM), GLP-1 (0.3 μm) and GIP (100 nM). AUC graphs represent area under the curve, analyzed by ANOVA with post-hoc Tukey test (A, D) or unpaired t test (G, H). For non-AUC graphs we used mixed-effects analysis with Tukey’s multiple comparisons. All data are represented as the mean ± SEM, ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001.