Mediation of hyperglycemia-evoked gastric slow-wave dysrhythmias by endogenous prostaglandins.
OBJECTIVE
Antral hypomotility and gastric dysrhythmias occur in diabetic gastroparesis. This study tested the hypothesis that acute hyperglycemia suppresses fed antral contractions and disrupts slow-wave rhythmicity via prostaglandin pathways.


METHODS
Six normal volunteers underwent electrogastrography and antroduodenal manometry under control, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions before and after administration of indomethacin (50 mg orally three 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 increase in arrhythmic activity (P < 0.05), whereas 140 and 175 mg/dL did 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 meal. Euglycemic, hyperinsulinemic clamping to insulin levels observed with 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 prevent the reduction in motility evoked by hyperglycemic clamping.


CONCLUSIONS
Acute hyperglycemia, but not hyperinsulinemia, inhibits fed antral motility and induces gastric dysrhythmias at higher plasma glucose levels. Induction of dysrhythmias, but not hypomotility, is dependent on endogenous prostaglandin synthesis. These findings offer insight into the myoelectric disturbances of diabetic gastroparesis and suggest a possible therapeutic role for prostaglandin synthesis inhibitors for gastric dysrhythmias in this condition.
Hasler
W L
WL
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Soudah
H C
HC
Dulai
G
G
Owyang
C
C
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004386:Duodenum / Q000503:physiopathology; D004594:Electrophysiology; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D008365:Manometry; D011453:Prostaglandins / Q000502:physiology*; D013270:Stomach / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D011453:Prostaglandins