Effect of Dexamethasone on Hepatic Glucose and Insulin Metabolism after Oral Glucose in Conscious Dogs

To examine whether hyperinsulinemia associated with gluco-corticoid treatment results solely from hypersecretion of insulin or also involves altered fractional hepatic extraction, oral glucose (1 g/kg body wt) was administered to dogs with or without dexa-methasone treatment (2 mg/d for 2 d). Dexamethasone signifi-cantly increased basal glucose and insulin concentrations in the portal vein, hepatic vein, and femoral artery, reduced basal frac-tional hepatic extraction of insulin from 43±4 % to 22±4%, and, after oral glucose, increased retention by the liver of net glucose released into the portal system from 27±4 % to 53±13%. Intra-portal insulin infusion (1 and 2 mU/kg per min) after 7 d of dexamethasone treatment (2 mg/d) caused less suppression of endogenous glucose prQduction, and less exogenous glucose was required to maintain an euglycemic clamp than in control animals. Dexamethasone treatment is associated with: (a) decreased basal fractional hepatic insulin extraction contributing to hyperinsu-linemia; and (b) less suppression of endogenous glucose produc-tion and increase in peripheral uptake in response to insulin, but no reduction in net hepatic glucose uptake after oral glucose