Automated Intestinal Electrical Stimulation for Diabetes

自动肠道电刺激治疗糖尿病

• 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
• 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

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）：糖尿病在2007年在美国影响超过1740亿美元的美国人的8％以上。最近，已经提出了减肥手术，例如Roux-en-Y胃搭桥术，用于治疗肥胖症患者的糖尿病患者，原因是其降血糖对餐后血糖的作用和显着的体重减轻。 在此提案中，我们提出了一种新型的自动肠电刺激（IES）治疗糖尿病的方法。基于我们小组的先前发表的研究，我们发现IES以类似于胃旁路程序的方式改变了胃肠道运动，生理和激素：它可以降低食物摄入和营养吸收，抑制胃ghrelin，从而在后固有状态下抑制胃gh蛋白并增加垂体状肽（GLPP-1）。基于这些发现，我们假设急性IES改善了餐后高血糖和慢性IES，从而改善了长期血糖控制。如果被证明有效，与减肥手术相比，提出的IE具有可调，可逆和侵入性较小的优点。 Goto-kakizaki（GK）大鼠是自发性2型糖尿病的最佳特征动物模型之一，并且在研究抗糖尿病手术的抗糖尿病机制中最广泛地使用了该项目的抗糖尿病机制，以证明遵循假设并在特定的目标之后实现后果。 1）优化IES方法，以使IE的降血糖作用最大化。特别是，IES的刺激参数将进行系统地研究和优化。将仔细检查急性优化IE对餐后血糖和胰岛素敏感性的影响。 2）研究急性IES降血糖作用涉及的可能机制。设计实验是为了测试IES诱导的餐后血糖降低的假设，通过延迟的胃排空和加速肠道传播机械地介导，并通过减少GHRELIN和GLP-1的释放来激素。 3）研究慢性IE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防止/减少慢性高血糖对β细胞功能和全身性胰岛素敏感性的有害影响，从而改善长期葡萄糖控制。将为慢性实验开发自动食品摄入算法。 一支多学科团队已组装以执行这项任务。 PI在胃肠道电刺激方面具有丰富的经验，这些经验在胃肠运动，肥胖症和糖尿病上具有丰富的经验。顾问Abate博士是胰岛素抵抗和糖尿病的专家。小型企业都有所有需要的专业知识和设施来设计和开发拟议的自动反馈控制的IES系统。