Deletion of both Tcf7l2 alleles potentiates the effects of Lkb1 deletion on glucose tolerance and insulin secretion in males. Oral glucose tolerance experiments were performed as described in Fig. 2 legend (A and B) (n = 7–11 mice/genotype). Insulin plasma levels were measured in vivo 2.5, 5, and 15 min after intraperitoneal injection of glucose (3 g/kg) (C and D) (n = 7–8 mice/genotype). E, insulin secretion in vitro was measured from groups of 10 size-matched isolated islets during static incubation (see “Experimental procedures”) and at the indicated glucose or KCl concentrations (n = 4–6 mice/genotype; *, p < 0.05; **, p < 0.01; ****, p < 0.0001). Gray open circles, βLkb1-KO-Tcf7l2-het; black filled circles, βLkb1-Tcf7l2-dKO. Error bars represent the mean ±S.E. AUC, area under the curve.