INDOMETHACIN STIMULATES BASAL GLUCOSE-PRODUCTION IN HUMANS WITHOUT CHANGES IN CONCENTRATIONS OF GLUCOREGULATORY HORMONES

1. To investigate whether indomethacin affects basal glucose productio n, we measured hepatic glucose production in six healthy postabsorptiv e subjects on two occasions: once after administration of indomethacin (150 mg orally) and once after administration of placebo. 2. Glucose production was measured by primed, continuous infusion of [3-H-3]-gluc ose. 3. Indomethacin administration resulted in an increase in glucose production from 10.9 (SEM 0.3) mumol min-1 kg-1 to a maximum of 16.5 (SEM 1.6) mumol min-1 kg-1 (P < 0.05) within approximately 1 h, wherea s in the control experiment glucose production declined gradually (P < 0.01) (P < 0.05 indomethacin versus control). There were no differenc es in plasma concentrations of insulin, C-peptide and counterregulator y hormones between the two experiments. 4. Since indomethacin administ ration resulted in an increase in glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclud e that indomethacin stimulates hepatic glucose production through othe r mechanisms.