Figure 4.

Mice with pancreas-specific MPC2 deletion have reduced GSIS despite normal insulin content. A: Immunohistochemical staining of islets showed no difference in immunodetectable insulin, glucagon, or β and α cell number. B: Histologic assessment of islet number and individual cross-sectional area detected no difference between WT and PdxCreMpc2−/− mice. C: Mice were fasted for 16 h and injected i.p. with 1.5 g/kg glucose. PdxCreMpc2−/− mice displayed significantly elevated blood glucose concentrations after the overnight fast and after bolus glucose injection. D: Mice were fasted for 4 h and injected i.p. with 0.5 U/kg insulin. PDXCreMpc2−/− mice displayed elevated basal blood glucose levels but similar insulin response curves. E: Plasma insulin concentrations were reduced in PdxCreMpc2−/− mice 15 min after bolus glucose injection. F: Loss of Mpc2 in beta cells impairs GSIS by isolated islets. Isolated islets from WT and PdxCreMpc2−/− mice were incubated with the indicated concentrations of glucose and insulin concentration of the medium determined. Insulin secretion was corrected in PdxCreMpc2−/− islets with either 1 μM glibenclamide treatment or stimulation with 30 mM KCl + 1 mM glucose. 10 mM glutamine + 23 mM glucose-stimulated insulin secretion was also normal. N = 10–12 mice per genotype with 10 pancreas sections analyzed per mouse in A and B. N = 10–13 mice per genotype in C and D. N = 5–6 mice per genotype in E. N = 2–3 mice per genotype and two technical replicates per mouse in F. Mean ± SEM is shown. P values comparing KOs to controls were calculated using a Student's t test. *p < 0.05, **p < 0.01, and ***p < 0.001, ^Ϯp < 0.05 compared to non-glib treatment.