Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, 21224, USA.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Obes Surg. 2021 May;31(5):1957-1966. doi: 10.1007/s11695-021-05228-w. Epub 2021 Jan 19.
Intestinal electrical stimulation (IES) has been reported to reduce body weight and improve glucose tolerance in obese and diabetic rats. Our study aimed to investigate possible IES mechanisms involving incretin hormones using intraduodenal glucose infusion in rats. We hypothesized that the enhanced release of postprandial glucagon-like peptide-1 (GLP-1) at early phase by IES was mediated through neuro/paracrine mechanisms involving the vagal nerve and glucose-dependent insulinotropic peptide (GIP).
Fifteen normal male Sprague-Dawley rats chronically implanted with duodenal electrodes for IES, and an intra-duodenum catheter for the infusion of glucose were studied in a series of sessions with IES of different parameters with and without atropine and M3 receptor antagonist. Blood samples were collected via the tail vein for the measurement of blood glucose, and plasma GLP-1, and GIP.
(1) Compared to sham-IES, IES of 0.3 ms reduced blood glucose by 16.5-28.4% between 30 and 120 min (all time points p < 0.05), and IES of 3-ms reduced blood glucose at 60 (12.6%) and 90 min (11.8%). IES of 0.3 ms showed a greater hypoglycemic effect than 3 ms (p = 0.024) at 30 min. (2) IES elevated plasma GLP-1 with 0.3 ms (p = 0.001) and with 3 ms p = 0.03). (3) IES substantially elevated plasma GIP with 0.3 ms (p = 0.002) and with 3 ms (p < 0.001). (4) Pretreatment of atropine and the M3 receptor antagonist 4-DAMP blocked the effects of IES on GLP-1, GIP, and blood glucose.
IES reduces postprandial blood glucose by enhancing the release of GLP-1 and GIP mediated via the cholinergic mechanism.
肠内电刺激 (IES) 已被报道可降低肥胖和糖尿病大鼠的体重并改善葡萄糖耐量。我们的研究旨在使用大鼠十二指肠内葡萄糖输注来研究涉及肠促胰岛素激素的可能 IES 机制。我们假设 IES 早期通过神经/旁分泌机制增强餐后胰高血糖素样肽 1 (GLP-1) 的释放，该机制涉及迷走神经和葡萄糖依赖性胰岛素释放肽 (GIP)。
15 只慢性植入十二指肠电极用于 IES 的正常雄性 Sprague-Dawley 大鼠，并在一系列具有和不具有阿托品和 M3 受体拮抗剂的不同参数的 IES 会议中使用十二指肠内导管进行葡萄糖输注。通过尾静脉采集血样，用于测量血糖和血浆 GLP-1 和 GIP。
(1) 与 sham-IES 相比，0.3ms 的 IES 在 30 至 120 分钟之间将血糖降低了 16.5-28.4%（所有时间点均 p<0.05），而 3ms 的 IES 在 60（12.6%）和 90 分钟（11.8%）时降低了血糖。在 30 分钟时，0.3ms 的 IES 比 3ms 的 IES 具有更大的降血糖作用（p=0.024）。(2) IES 升高了血浆 GLP-1，0.3ms（p=0.001）和 3ms（p=0.03）。(3) IES 显著升高了血浆 GIP，0.3ms（p=0.002）和 3ms（p<0.001）。(4) 阿托品预处理和 M3 受体拮抗剂 4-DAMP 阻断了 IES 对 GLP-1、GIP 和血糖的影响。
IES 通过胆碱能机制增强 GLP-1 和 GIP 的释放来降低餐后血糖。
