Intestinal Electrical Stimulation Synchronized With Intestinal Slow Wave Ameliorates Glucagon-Induced Hyperglycemia in Rats.

Background: Synchronized intestinal electrical stimulation (SIES), in which intestinal electrical stimulation (IES) is delivered in synchronization with the intrinsic slow wave of small intestine, was previously reported to be more potent in accelerating small intestine transit than IES delivered at fixed frequency and phase. We hypothesized that SIES is more potent in suppressing postprandial blood glucose by enhancing the release of glucagon-like peptide-1 (GLP-1) and insulin.

Materials And Methods: Rats underwent long-term implant of two pairs of electrodes at the duodenum for IES and SIES, respectively. Acute hyperglycemia was induced with glucagon, and the oral glucose tolerance test was performed on separate days with IES, SIES, or sham (no stimulation).

Results: 1. Glucagon reduced the percentage of normal slow wave in sham (70.9% ± 4.1%) from (84.9% ± 2.6%, p = 0.006) of control, which was ameliorated by SIES (82.5% ± 3.3%, p = 0.031). 2. IES and SIES reduced glucagon-induced increase of blood glucose (192 mg/dl) at 30 minutes by 17% and 20%, respectively. SIES showed a further inhibitory effect at 60 minutes (147 vs 171 mg/dl, p = 0.003, vs sham). 3. Compared with sham (139 pg/ml), GLP-1 at 30 minutes was increased in both IES (158 pg/ml) and SIES (169 pg/ml). GLP-1 level was still high at 60 minutes in rats with SIES. 4. At 30 minutes, the plasma insulin level was increased by 18.8 μIU/ml with SIES, which was significantly higher than that with sham (7.1 μIU/ml, p < 0.001) and IES (13.2 μIU/ml, p = 0.041).

Conclusion: SIES is more effective than IES in reducing glucagon-induced acute hyperglycemia by enhancing the release of GLP-1 and insulin.