Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine

Abstract

Proximal and distal rat small intestine from control, diabetic, and insulin-treated diabetic rats was cut into strips measuring 6.0 × 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, while those cut 90 ° to that axis were called circular strips. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1–1.0-ms pulse duration, 30–270 mA, 1–26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10−6 M atropine. Field stimulation produced atropine-sensitive and atropineresistant contractions in all strips. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from distal longitudinal muscle. Controls showed the highest amplitude contractions and diabetics the lowest, whereas the insulin-treated diabetics showed contractions intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 ms in the presence of neural blockade with tetrodotoxin (5 × 10−6 M) produced similar contraction amplitudes among the three groups. These results suggest that streptozotocin-induced diabetes mellitus is associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. Insulin therapy seems to improve the abnormality.