Automated Intestinal Electrical Stimulation for Diabetes

自动肠道电刺激治疗糖尿病

基本信息

批准号：
8589929
负责人：
Jiande Chen
金额：
$ 20.03万
依托单位：
TRANSTIMULATION RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-17 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8589929
关键词：
Abate Acceleration Acute Affect Algorithms American Animal Model Animals Beta Cell Blood Glucose Body Weight Body Weight decreased Businesses Bypass Cell physiology Characteristics Chronic Controlled Study Detection Development Diabetes Mellitus Disease Disease remission Distal Down-Regulation Duodenum Eating Electric Stimulation Electrodes Exclusion Feedback Gastric Bypass Gastric Emptying Gastrointestinal Motility Gastroparesis Glucose Goals Heart Diseases Hormones Human Hyperglycemia Hypoglycemia Insulin Resistance Intestinal Absorption Intestines Kidney Failure Mediating Medical Methodology Methods Non-Insulin-Dependent Diabetes Mellitus Nutrient Obesity Oral Patients Phase Physiology Procedures Publishing Rattus Safety Series Small Intestines Stomach Stroke System Testing Work absorption bariatric surgery base blood glucose regulation cost design diabetic diabetic patient diabetic rat experience gastrointestinal ghrelin glucagon-like peptide glycemic control improved insulin sensitivity jejunum novel prevent public health relevance research study

项目摘要

DESCRIPTION (provided by applicant): Diabetes affects more than 8% of Americans and costs over $174 billion in 2007 in USA. Recently bariatric surgery, such as Roux-en-Y gastric bypass, has been proposed for treating diabetic patients with obesity due to its hypoglycemic effect on postprandial blood glucose and significant weight loss. In this proposal, we propose a novel method of automated intestinal electrical stimulation (IES) for the treatment of diabetes. Based on previous published studies in our group, we have discovered that IES alters gastrointestinal motility, physiology and hormones in a way similar to the gastric bypass procedure: it reduces food intake and nutrient absorption, inhibits gastric ghrelin and increases glucagon-like peptide (GLP-1) in the postprandial state. Based on these findings, we hypothesize that acute IES improves postprandial hyperglycemia and chronic IES results in improvement in long-term glycemic control. If proven effective, the proposed IES has advantages of being adjustable, reversible and less invasive, compared with bariatric surgery. The Goto-Kakizaki (GK) rat, one of the best characterized animal models of spontaneous Type 2 diabetes and most widely used in studying anti-diabetic mechanisms of bariatric surgeries will be used in this project to prove following hypotheses and accomplish following specific aims. 1) To optimize IES methodology such that the hypoglycemic effect of IES is maximized. Particularly, the stimulation parameters of IES will be systematically investigated and optimized. The effects of acute optimized IES on postprandial blood glucose and insulin sensitivity will be carefully examined. 2) To investigate possible mechanisms involved in the hypoglycemic effect of acute IES. Experiments are designed to test the hypothesis that IES-induced reduction in postprandial blood glucose is mediated mechanically by delayed gastric emptying and accelerated intestinal transit, and hormonally by reduced ghrelin and increased release of GLP-1. 3) To study effects and mechanisms of chronic IES on long-term glycemic control. Chronic experiments are designed to test the hypothesis that improvement in postprandial hyperglycemia prevents/reduces the detrimental effect of chronic hyperglycemia on beta-cell function and systemic insulin sensitivity, leading to improvement of long-term glucose control. An automatic food intake detection algorithm will be developed for the chronic experiments. A multi-disciplinary team has been assembled to undertake the task. The PI has extensive experience in gastrointestinal electrical stimulation on gastrointestinal motility, obesity and diabetes. The consultant Dr. Abate is an expert from in insulin resistance and diabetes. The small business has all required expertise and facilities to design and develop the proposed automatic feedback controlled IES system.

描述（由申请人提供）：糖尿病影响着超过 8% 的美国人，2007 年在美国造成的损失超过 1,740 亿美元。最近，减肥手术，如Roux-en-Y胃绕道手术，因其对餐后血糖的降血糖作用和显着的体重减轻而被提议用于治疗肥胖的糖尿病患者。在这项提案中，我们提出了一种用于治疗糖尿病的自动肠道电刺激（IES）的新方法。根据我们小组之前发表的研究，我们发现IES以类似于胃绕道手术的方式改变胃肠动力、生理和激素：它减少食物摄入和营养吸收，抑制胃饥饿素并增加胰高血糖素样肽（GLP） -1) 餐后状态。基于这些发现，我们假设急性 IES 可改善餐后高血糖，而慢性 IES 可改善长期血糖控制。如果证明有效，与减肥手术相比，所提出的IES具有可调节、可逆和侵入性较小的优点。 Goto-Kakizaki (GK) 大鼠是自发性 2 型糖尿病特征最好的动物模型之一，在研究减肥手术的抗糖尿病机制中应用最广泛，将在本项目中用于证明以下假设并实现以下特定目标。 1）优化IES方法，使IES的降糖效果最大化。特别是，IES的刺激参数将被系统地研究和优化。将仔细检查急性优化 IES 对餐后血糖和胰岛素敏感性的影响。 2) 研究急性IES降血糖作用的可能机制。实验旨在检验以下假设：IES 诱导的餐后血糖降低是通过延迟胃排空和加速肠道运输机械介导的，以及通过减少 ghrelin 和增加 GLP-1 释放的激素介导的。 3) 研究慢性IES对长期血糖控制的影响和机制。慢性实验旨在检验以下假设：餐后高血糖的改善可以预防/减少慢性高血糖对β细胞功能和全身胰岛素敏感性的有害影响，从而改善长期血糖控制。将为长期实验开发自动食物摄入检测算法。已经组建了一个多学科团队来承担这项任务。 PI在胃肠电刺激治疗胃肠动力、肥胖和糖尿病方面拥有丰富的经验。顾问阿巴特博士是胰岛素抵抗和糖尿病方面的专家。该小型企业拥有设计和开发拟议的自动反馈控制 IES 系统所需的所有专业知识和设施。