Small Intestinal Slow Wave Dysrhythmia and Blunted Postprandial Responses in Diabetic Rats

Abstract

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 type 2 diabetes induced by high-fat diet feeding followed by a low dose of streptozotocin (30 mg/kg) and normal rats. The percentage of normal slow wave (%NSW), dominant power, and dominant frequency (DF) were assessed from the IMA under various conditions. Oral glucose tolerance test was performed, and blood was collected via the tail vein at baseline and 15, 30, 60, 90, 120, and 180 min after glucose administration for the measurement of blood glucose. 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 (p = 0.007), diabetic rats showed a blunted postprandial response in DF (p = 0.145) 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 = 0.004, N = 8) as well as HbA1C (r = -0.871, p = 0.005, N = 8). After glucose administration, the increase in blood glucose was correlated with a decrease in %NSW (r = -0.655, p < 0.001, N = 8). (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.

Keywords: diabetes; gastrointestinal motility; hyperglycemia; small intestinal slow wave.

FIGURE 1

Experimental surgeries and flow diagrams of experimental protocols. (a) Schematic figure of animal surgeries and tests performed on adult rats. (b) Flow diagram of experimental protocol. Regular, regular chow; HFD, high‐fat diet; liquid meal, ensure; solid meal, regular chow.

FIGURE 2

Comparisons of intestinal slow waves with regular chow between normal (n = 6) and diabetic rats (n = 6). (a) The percentage of normal small intestinal slow waves in fasting and fed states. (b) Dominant frequency of small intestinal slow waves. (c) Dominant power of small intestinal slow waves. *p < 0.05 versus fasting.

FIGURE 3

Comparisons of intestinal slow waves with HFD between normal (n = 6) and diabetic rats (n = 6). (a) The percentage of normal small intestinal slow waves in fasting and fed states. (b) Dominant frequency of small intestinal slow waves. (c) Dominant power of small intestinal slow waves. *p < 0.05 versus fasting.

FIGURE 4

Correlation of intestinal slow waves with blood glucose in diabetic rats (n = 8). (a) Correlation between the percentage of normal slow waves and blood glucose in fasting state in diabetic rats. (b) Correlation between the percentage of normal slow waves and HbA1c in fasting state in diabetic rats.

FIGURE 5

Blood glucose and regularity of intestinal slow waves after oral glucose administration (n = 8). (a) Correlation between the percentage of normal small intestinal slow waves and increase in blood glucose after oral glucose administration. (b) Increase in blood glucose and decrease in percentage of normal slow waves. Compared with 0 min blood glucose, **p < 0.01, *p < 0.05. Compared with 0 min %NSW, p > 0.05 at each time point. (c) Typical slow wave tracings relative to blood glucose levels (lower) compared with the fasting state (upper).

FIGURE 6

Temporal changes in duodenal slow wave parameters during the 180‐min period after an oral glucose load in diabetic rats (n = 8). (a) Percentage of normal slow waves, (b) Dominant frequency of slow waves, and (c) Dominant power of slow waves. 0 min: fasting data; 15–180 min: 15–180 min after the oral glucose load.

FIGURE 7

Blunted postprandial response of intestinal slow waves either with regular chow or HFD in diabetic rats (n = 6). (a) Percentage of normal small intestinal slow waves, (b) Dominant frequency of small intestinal slow waves, and (c) Dominant power of small intestinal slow waves.

FIGURE 8

Blunted postprandial response of intestinal slow waves either with solid or liquid meal in diabetic rats (n = 6). (a) Percentage of normal small intestinal slow waves, (b) Dominant frequency of small intestinal slow waves, and (c) Dominant power of small intestinal slow waves.

FIGURE 9

Blunted postprandial response of intestinal slow waves either with large or small liquid meal in diabetic rats (n = 6). (a) Percentage of normal small intestinal slow waves, (b) Dominant frequency of small intestinal slow waves, and (c) Dominant power of small intestinal slow waves.