Use of a bio-electronic device comprising of targeted dual neuromodulation of the hepatic and celiac vagal branches demonstrated enhanced glycemic control in a type 2 diabetic rat model as well as in an Alloxan treated swine model

作者：Jonathan J. Waataja, Raj K. Nihalani, Chris N. Honda, Charles J. Billington · 发表于：Frontiers in Neuroscience · 年份：2022 · DOI：10.3389/fnins.2022.1005932 · 被引用次数：10 · 研究领域：Vagus Nerve Stimulation Research、Heart Rate Variability and Autonomic Control、Diabetes Management and Research

Background: There is an unmet need for new type 2 diabetes treatments providing improved efficacy, durability and customized to improve patient's compliance. Bio-electronic neuromodulation of Vagus nerve branches innervating organs that regulate plasma glucose, may be a method for treating type 2 diabetes. The pancreas has been shown to release insulin during Vagus stimulation. The hepatic vagal branch, innervating the liver, has been shown to decrease glucose release and decrease insulin resistance following ligation. However, standalone stimulation of the Vagus nerve has shown mixed results and Vagus nerve ligation has undesirable effects. Little is known; however, of the effect on plasma glucose with combined neuromodulation consisting of stimulation of the celiac branch innervating the pancreas with simultaneous high frequency alternating current (HFAC) blockade of the hepatic branch. This study tested the effects of this approach on increasing glycemic control in rat a model of type 2 diabetes and Alloxan treated swine. Materials and methods: Zucker obese (fatty) male rats (ZDF fa/fa) were used as a model of type 2 diabetes as well as glucose intolerant Alloxan treated swine. In ZDF rat experiments glycemic control was accessed with an intravenous glucose tolerance test during HFAC-induced hepatic branch block with concurrent celiac stimulation (HFAC + stimulation). In swine experiments glycemic control was accessed by an oral glucose tolerance test during HFAC + stimula...