iGluCreLepRKOmice display normal glucose tolerance and fasting blood glucose levels. (A) Body weight followed for 30 weeks in male (green) and female (red) iGluCreLepRKO and LepRF/F mice (n = 12–19 mice per genotype). (B) Fasting blood glucose levels in 8 week old males and females (n = 6–11 mice per genotype). (C,D) Blood glucose concentration after IPGTT in male and female iGluCreLepRKO (square symbol) and LepRF/F (green triangle) mice. Blood glucose concentration after ITT in males: (E) iGluCreLepRKO, n = 8, LepRF/F, n = 7; and females: (F) iGluCreLepRKO, n = 8, LepRF/F, n = 10. Plasma glucagon levels during ITT, iGluCreLepRKO, n = 6, LepRF/F, n = 4, (G), and glucagon release from isolated islets in the presence of the indicated glucose concentrations: LG = 0.5 mM, HG = 10 mM glucose; n = 6 animals per genotype (H). When present, leptin was added to 10 nM. Data are expressed as the mean ± SEM and statistical comparison was through two-way ANOVA, *p < 0.05. Other details are provided in the Materials and Methods section.