Figure 6. Inappropriate plasma glucagon levels are corrected in Leprlox^TB × POMC-cre mice, and this contributes to improvements in hepatic insulin action.

(A) Shown are body weight and 12-hour–fasted/carbohydrate-refed plasma glucagon (B) as well as insulin (C) in WT, WT expressing Cre-recombinase in POMC neurons, leptin receptor LEPR-null mice generated by inserting floxed transcription blocking sequences in the Lepr gene (Leprlox^TB), and littermates in which LEPRs are selectively reactivated in POMC neurons (Leprlox^TB × POMC-cre) (n = 8–10 mice/genotype). (D and E) Pancreatic glucagon and insulin content, respectively (n = 12–15 mice/genotype). (F) Blood glucose during 120-minute hyperinsulinemic-euglycemic (25 mU/kg/min, 150 mg/dl, respectively) clamps plus somatostatin (9 ng/kg/min) in conscious, chronically catheterized, 4- to 5-hour–fasted, 8- to 9-week-old male mice (n = 6 mice/genotype). (G) GIR is shown. (H and I) Basal and clamp plasma glucagon and insulin, respectively, are shown. (J and K) Basal and insulin-stimulated (clamp steady-state [t = 80–120 minutes]) glucose production and disposal determined using [3-³H]glucose are shown. *P < 0.05, comparing Leprlox^TB to Leprlox^TB × POMC-cre mice; ^†P < 0.05, comparing WT controls to Leprlox^TB mice; ^#P < 0.05 comparing fed and refed mice; ^‡P < 0.05, comparing clamp to basal with a genotype. Data are presented as mean ± SEM.