(a, b) Male Leprcre mice were injected bilaterally with the activating DREADD hM3Dq and allowed to recover for at least two weeks. Animals were injected with Proglumide (PG; 20 mg/kg, IP) or Vehicle (Veh) and 30 minutes later were injected with vehicle or CNO (0.3 mg/kg, IP) and (a) blood glucose was monitored at the indicated times; {F(3,16)=6.19}, N=3(v/v), 3 (pg/v), 7(v/c), and 7 (pg/c) animals. (b) Hepatic G6Pase mRNA expression (fold over control) was measured at the end of the experiment; p<0.001 from all groups {F(3,13)=21.839}, N=5 (v/v), 4 (pg/v), 4 (v/c), and 4 (pg/c) animals. Aall data are plotted as mean +/− SEM (c) C57Bl/6 mice were injected with Proglumide (PG; 100 mg/kg, IP) or Vehicle and 30 minutes later were injected with vehicle or 2DG (500 mg/kg, IP) and blood glucose was monitored at the indicated times; {F(3,25)=43.47}, N=6 (v/v), 7 (pg/v), 8 (v/2dg), and 8 (pg/2dg) animals. All data are plotted as mean +/− SEM. The data included in panels a and c were analyzed by two way repeated measures ANOVA with Fisher LSD post hoc test; the data in panel b was analyzed by one way ANOVA with Fisher LSD post hoc test. A:*p=0.006 vs(PG/Veh), 0.001 vs (PG/CNO), and 0.031 vs (Veh/Veh). C:*p<0.001 vs all groups.