MODULATION OF GLUCOSE-PRODUCTION BY INDOMETHACIN AND PENTOXIFYLLINE IN HEALTHY HUMANS

Indomethacin, an inhibitor of prostaglandin synthesis that modulates c ytokine production, increases hepatic glucose output (HGO) in humans. However, prostaglandins stimulate glucose production in vitro. To inve stigate the mechanism of HGO stimulation by indomethacin, we compared the effect of pentoxifylline, an inhibitor of cytokine production, ver sus saline (study 1, n = 6) and of indomethacin versus the combination of indomethacin and pentoxifylline (study 2, n = 5) on basal HGO. HGO was measured by primed, continuous infusion of 3-H-3-glucose. In stud y 1, pentoxifylline infusion resulted in an immediate, transient decre ase of HGO of approximately 50% (from 12.9 +/- 0.4 to 6.0 +/- 1.7 mu m ol/kg/min after 15 minutes, P < .03 v control). There were no differen ces in concentrations of glucoregulatory hormones between the two expe riments, in study 2, after indomethacin administration, HGO increased transiently by approximately 84% (from 9.7 +/- 0.7 at baseline to 16.7 +/- 2.4 mu mol/kg/min after 135 minutes, P < .05). However, pentoxify lline did not affect the increase in HGO induced by indomethacin. Ther e were no differences in concentrations of glucoregulatory hormones be tween the two experiments. Therefore, indomethacin stimulates HGO by m echanisms unrelated to glucoregulatory hormones, prostaglandins, or cy tokines. Copyright (C) 1996 by W.B. Saunders Company