FIGURE 5.

Knockdown of p110γ impairs GIP-amplified insulin secretion from mouse islets and exocytosis from mouse β-cells. A, insulin secretion was measured by perifusion of isolated mouse islets infected with Adsh-scram (open circles) or Adsh-p110γ (black circles). 16.7 mmol/liter glucose was perifused at 10 min. B, shows the same as A, except cells were additionally perifused with GIP (100 nmol/liter; added at 10 min). C, static insulin secretion was measured from human islets infected with Adsh-scram or Adsh-p110γ in response to high glucose alone (open bars) or with 100 nmol/liter GIP (gray bars), shown as the stimulation index (fold increase over a low glucose control). HG, 10 mmol/liter glucose-stimulated. D, representative capacitance recordings (left panel) and averaged cumulative capacitance responses (right panel) from mouse β-cells infected with Adsh-scram (gray lines, open circles) or Adsh-p110γ (black lines, black circles). E, shows the same as C, except cells were additionally treated with GIP (100 nmol/liter; 1 h). F, representative capacitance recordings (left panel) and averaged cumulative capacitance responses (right panel) from mouse β-cells transfected with si-scram (gray lines, open circles) or si-p110γ (black lines, black circles). The mRNA expression of p110γ (normalized to cyclophilin) following transfection with si-scram (open bar) or si-p110γ (black bar) is shown inset. G, shows the same as F, except cells were additionally treated with GIP (100 nmol/liter; 1 h). *, p < 0.5; **, p < 0.01; ***, p < 0.001.