Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Neuromodulation. 2022 Dec;25(8):1097-1105. doi: 10.1111/ner.13367. Epub 2022 Feb 15.
Intestinal electrical stimulation (IES) has been proposed for treating diabetes; however, its parameters need to be further systematically optimized. This study aimed to optimize the parameters of IES and investigate its possible mechanisms involving glucagon-like peptide-1 (GLP-1) in diabetic rats.
Thirty-six high-fat diet-induced diabetic rats were chronically implanted with a pair of bipolar electrodes at the duodenum for IES. The oral glucose tolerance test (OGTT) was performed in a number of sessions with IES using different parameters and biphasic charge-balanced waveforms to derive the best values for train on-time, pulse frequency, and pulse width. Incretin hormones such as GLP-1 were assessed and the GLP-1 antagonist Exendin 9-39 was used to assess the role of GLP-1 in the ameliorating effect of IES on hyperglycemia.
The most effective IES parameters in reducing blood glucose (BG) during the OGTT were derived: 1.2 sec on, 0.3 sec off, 80 Hz, 3 msec. IES with these parameters reduced BG level by at least 29% from 15 min to 180 min (p < 0.05 for all points, N = 10). IES with these stimulation parameters increased plasma GLP-1 level at 30 min, 60 min, 90 min and gastric inhibitory peptide (GIP) level at 30 min (N = 8). Exendin 9-39 blocked the inhibitory effect of IES on BG (p > 0.05, IES + Exendin 9-39 vs sham-IES, N = 8).
IES with the most effective parameters derived in this study improves hyperglycemia in diabetic rats. The ameliorating effect of IES on hyperglycemia is attributed to the enhanced release of GLP-1. IES has great potential for treating diabetes.
肠道电刺激（IES）已被提议用于治疗糖尿病，但需要进一步系统地优化其参数。本研究旨在优化 IES 参数，并研究其可能涉及胰高血糖素样肽-1（GLP-1）的机制，以治疗糖尿病大鼠。
36 只高脂肪饮食诱导的糖尿病大鼠接受了一对双极电极的慢性植入，用于 IES。使用不同的参数和双相平衡电荷波形进行了多次口服葡萄糖耐量试验（OGTT），以得出最佳的训练时间、脉冲频率和脉冲宽度值。评估了肠降血糖素激素，如 GLP-1，并使用 GLP-1 拮抗剂 Exendin 9-39 评估 GLP-1 在 IES 改善高血糖中的作用。
得出了在 OGTT 期间降低血糖（BG）最有效的 IES 参数：1.2 秒 ON，0.3 秒 OFF，80 Hz，3 msec。这些参数的 IES 将 BG 水平降低了至少 29%，从 15 分钟到 180 分钟（所有时间点均为 p < 0.05，N = 10）。这些刺激参数的 IES 在 30 分钟、60 分钟、90 分钟时增加了血浆 GLP-1 水平，在 30 分钟时增加了胃抑制肽（GIP）水平（N = 8）。Exendin 9-39 阻断了 IES 对 BG 的抑制作用（p > 0.05，IES + Exendin 9-39 与 sham-IES，N = 8）。
本研究中得出的最有效参数的 IES 改善了糖尿病大鼠的高血糖。IES 对高血糖的改善作用归因于 GLP-1 的释放增强。IES 具有治疗糖尿病的巨大潜力。
