INTESTINAL SLOW WAVE DYSRHYTHMIA AND BLUNTED POSTPRANDIAL RESPONSES IN DIABETIC RATS

Background: Gastric dysmotility and gastric slow wave dysrhythmias have been well documented in patients with diabetes. However, little is known on the effect of hyperglycemia on small intestine motility such as intestinal slow waves, due to limited options in measuring its activity. Moreover, food intake and digestion process have been reported to alter the small intestine motility in normal rats, but their roles in that of diabetic rats remains unknown. This study aimed to explore the effect of hyperglycemia on small intestinal myoelectrical activity (IMA) and responses to various meals in diabetic and normal rats.
Methods: IMA was recorded via chronically implanted serosal electrodes in the proximal small intestine in rats with diabetes induced by high-fat diet feeding followed by a low dose of streptozotocin (STZ, 30 mg/kg) and normal rats. The percentage of normal slow wave (% NSW) and dominant frequency (DF) were assessed from IMA under various conditions. Oral glucose tolerance test (OGTT, 20% glucose, 1 g/kg) was performed and blood was collected via the tail vein at baseline and 15, 30, 60, 90, 120, 180 min after glucose administration for the measurement of blood glucose. The correlations of blood glucose with NSW and DF were determined. Regular laboratory chow, high-fat diet, and small or large nutrient liquid meal were used to explore IMA responses to different meals in diabetic and normal rats.
Results: (1) Compared with a postprandial increase in DF in normal rats (40.3±1.4 vs. 42.2±0.7 cycles/min (CPM), vs. Fasting, P=0.001, N=6), diabetic rats showed a blunted postprandial response in DF (39.4±3.7 vs. 39.9±3.1 vs. Fasting, P>0.05, N=8) after a regular chow. However, no difference was found in % NSW between diabetic and normal rats in both fasting and fed states; (2) In the fasting state, % NSW was correlated with the blood glucose level in diabetic rats (r=-0.817, P<0.001, Fig.1a) as well as HbA1C (r=-0.871, P=0.005). After glucose administration, the increase in blood glucose was correlated with a decrease in % NSW (r=-0.647, P<0.001, Fig.1b). (3) % NSW in diabetic rats during the 30-min postprandial state was not altered after a meal, either liquid or solid, regular or high-fat diet, small or large meal, suggesting an absence of gastric-small intestinal reflex.
Conclusions: In type 2 diabetic rats, the regularity of intestinal slow waves is negatively correlated with the blood glucose level in both fasting and fed states. Diabetic rats exhibit a blunted postprandial response in intestinal slow waves compared with normal rats. There seems to be a lack of gastric-small intestinal reflex upon food ingestion in diabetic rats. (This study was supported by an NIH grant, R01DK107754)