MEDIATION OF HYPERGLYCEMIA-EVOKED GASTRIC SLOW-WAVE DYSRHYTHMIAS BY ENDOGENOUS PROSTAGLANDINS

Background/Aims: Antral hypomotility and gastric dysrhythmias occur in diabetic gastroparesis. This study tested the hypothesis that acute h yperglycemia suppresses fed antral contractions and disrupts slow-wave rhythmicity via prostaglandin pathways. Methods: Six normal volunteer s underwent electrogastrography and antroduodenal manometry under cont rol, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp condi tions before and after administration of indomethacin (50 mg orally th ree times daily for 3 days). Results: Hyperglycemic clamping to 230 mg /dL evoked a 4-fold increase in tachygastric activity and a 2.6-fold i ncrease in arrhythmic activity (P < 0.05), whereas 140 and 175 mg/dL d id not induce dysrhythmias. Antral motility indexes were reduced by 58 % +/- 14% at 175 mg/dL and 70% +/- 8% at 230 mg/dL after a 750-kcal me al. Euglycemic, hyperinsulinemic clamping to insulin levels observed w ith the highest glucose infusions did not produce tachyarrhythmias or hypomotility. After indomethacin, hyperglycemic clamping to 230 mg/dL did not induce tachyarrhythmias. In contrast, indomethacin did not pre vent the reduction in motility evoked by hyperglycemic clamping. Concl usions: Acute hyperglycemia, but not hyperinsulinemia, inhibits fed an tral motility and induces gastric dysrhythmias at higher plasma glucos e levels. Induction of dysrhythmias, but not hypomotility, is dependen t on endogenous prostaglandin synthesis. These findings offer insight into the myoelectric disturbances of diabetic gastroparesis and sugges t a possible therapeutic role for prostaglandin synthesis inhibitors f or gastric dysrhythmias in this condition.