Figure 3.

Impaired insulin secretion and exocytosis to glucose and incretins from male pSENP1-KO mice following HFD. A: Representative immunostaining and quantification of β-cell mass, islet number, and islet size distribution in male pSENP1-WT (n = 5 mice, 15 sections, and 220 islets) and pSENP1-KO (n = 3 mice, 9 sections, and 116 islets) pancreas following HFD. B: β-Cell exocytosis, following HFD, elicited by a series of 500-ms membrane depolarization from −70 mV to 0 mmol/L in the presence of 5 mmol/L glucose alone and together with Ex4 (10 nmol/L) or GIP (100 nmol/L) (n = 24–42 cells from 3–5 pairs of male mice). cAMP was omitted from the pipette solution. C: Average integrated Ca²⁺ currents elicited by a single 500-ms membrane depolarization from −70 mV to 0 mmol/L at 5 mmol/L glucose or with Ex4 or GIP (n = 21–48 cells). cAMP was omitted in pipette solution. D and E: Insulin secretion from male pSENP1-WT and -KO islets following HFD in response to glucose alone (n = 8 and 6) (D and E) or together with Ex4 (10 nmol/L) (n = 7 and 6) (D) or GIP (100 nmol/L) (n = 6 and 6) (E). F: Area under the curve (AUC) during the glucose stimulation from D and E. Data are mean ± SEM and were compared using Student t test or one-way or two-way ANOVA followed by Bonferroni posttest. *P < 0.05, **P < 0.01, ***P < 0.001 compared with the control condition. In panels D and E, we show significance comparing the pSENP1-WT and -KO in the presence of Ex4 or GIP only.