Figure 3.

Selective overexpression of CB₁ in the liver is associated with hepatic insulin resistance and reduced insulin clearance. (A) HtgCB₁^−/− mice on STD (filled columns) are hyperglycemic and show hepatic insulin resistance, compensated by increased whole body glucose uptake, relative to CB₁^−/− littermates (open columns). (B) Plasma insulin before (basal) and 120 minutes after initiation of euglycemic/hyperinsulinemic clamp. *P < .05, ^**P < .01 relative to corresponding value in CB₁^−/− mice, n = 7 (CB₁^−/−) or 8 (htgCB₁^−/−). (C) Plasma levels of human insulin, measured in the same “clamp” samples, *P < .05. (D) Plasma levels of C-peptide in same basal and clamp samples. (E) IDE and p-CEACAM1 levels and IDE activity in livers from CB₁^−/− and htgCB₁^−/− mice.