Effects of Abscisic Acid on Insulin Sensitivity

脱落酸对胰岛素敏感性的影响

• 批准号: 10202581
• 负责人: Raquel Hontecillas
• 金额: $ 42万
• 依托单位: BIOTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10202581
• 关键词: Abscisic Acid; Address; Adipocytes; Adult; American; Animals; Antidiabetic Drugs; Biological Response Modifier Therapy; Biopsy; Blood; Blood Glucose; Cells; Centers for Disease Control and Prevention (U.S.); Characteristics; Clinical Research; Computer Models; Consumption; Cross-Over Trials; Data; Development; Diabetes Mellitus; Diabetic mouse; Diet; Dose; Fatty acid glycerol esters; Fruit; GLUT 4 protein; Glucose; Glucose Clamp; Glucose Intolerance; Glycogen; Goals; Health; Human; Human body; Inflammation; Insulin; Insulin Resistance; Intake; Intellectual Property; Legal patent; Life Style; Medical; Metabolic; Metabolic syndrome; Methods; Mus; Muscle; Muscle Cells; Muscle Fibers; Myoblasts; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Outcome; Patients; Persons; Phase; Placebos; Plasma; Population; Prediabetes syndrome; Production; Randomized; Rattus; Recommendation; Role; Signal Transduction; Site; Skeletal Muscle; Small Business Innovation Research Grant; Small Interfering RNA; Specificity; Structure of beta Cell of islet; Supplementation; Symptoms; Toxicology; Translations; Type 2 diabetic; Virginia; Water; base; blood glucose regulation; commercial application; conditional knockout; diabetic; dietary; feeding; fruits and vegetables; glucose disposal; glucose metabolism; glucose tolerance; glucose uptake; glycemic control; improved; innovation; insulin sensitivity; insulin signaling; knockout animal; medical food; nutrition; oxidation; placebo controlled trial; research and development; side effect; translational study; uptake

Effects of Abscisic Acid on Insulin Sensitivity Biotherapeutics Inc (BTI), a spinoff Company of Virginia Tech, is developing innovative products for personalized nutrition. BTI has licensed 11 patent applications from Virginia Tech related to new methods of lowering blood sugar levels and suppressing inflammation during prediabetes and type 2 diabetes, including significant intellectual properties (IP) on the anti-diabetic actions of abscisic acid (ABA). We developed an ABA extract from figs (ABAlife™) and established ABA as a Generally Regarded as Safe (GRAS) ingredient. Significance & Product: Prediabetes afflicts 86 million Americans and has recently risen to more than 3 million new cases per year in the U.S. alone. A prediabetic person is likely to become diabetic within 10 years, because many people with prediabetes have no symptoms and do not adhere to lifestyle and diet changes or medical treatment. According to the CDC, 9 out of 10 Americans with prediabetes don’t know they have it. Dietary ABA supplementation is a safe and non-toxic method to improve glycemic control in mice, rats, and humans with an effective dose as low as 1 µg/kg and no side effects. The goal of this Fast-Track proposal is to develop ABA as a medical food ingredient for glycemic control. The Specific Aims for the SBIR Fast-Track Phase I application are to: AIM 1. Validate the mechanisms of action and cell specificity of dietary ABA in skeletal muscle of mice. We will investigate differential ABA-induced LANCL2 signaling in skeletal muscle cells during diabetes. We will employ LANCL2 conditional knockout animals to address ABA’s cell-specific effects. AIM 2. Characterize the potential for translation of LANCL2-dependent mechanism in human primary skeletal muscle cells. Under ABA or vehicle treated conditions, with or without siRNA/CRISP LANCL2, we will assess GLUT4 translocation, glucose uptake and oxidation, and glycogen synthesis. Transition Milestones are: ABA is dependent on muscle-specific expression of LANCL2 and ABA induces increases in the uptake and metabolism of glucose in mice and ex vivo culture of primary human muscle cells. The Specific Aims for the SBIR Fast-Track Phase II application are to: AIM 3. Perform a 14-day human clinical study in prediabetic subjects to assess the effects of ABA on glucose homeostasis and tolerability. Using a two group, randomized, placebo controlled crossover trial, we will evaluate how ABA (95 μg) twice daily effects insulin sensitivity within skeletal muscle by the hyperinsuliemic, euglycemic clamp, combined with percutaneous muscle biopsies to directly interrogate LANCL2 activation and GLUT4 translocation in enhanced insulin sensitivty. Commercial Application: BTI will have generated claims for ABA in maintaining healthy glucose levels. ABA products could disrupt the $9B medical food, 15B functional water, and $58B diabetes markets by 2018.

脱落酸对胰岛素敏感性的影响 Biotherapeutics Inc（BTI）是弗吉尼亚理工大学的一家分拆公司，正在开发创新产品， 个性化营养BTI已授权弗吉尼亚理工大学的11项专利申请，涉及新的方法， 在糖尿病前期和2型糖尿病期间降低血糖水平和抑制炎症，包括 关于脱落酸（阿坝）的抗糖尿病作用的重要知识产权（IP）。我们开发了一个阿坝 无花果提取物（ABAlife™），并确立阿坝为一般公认安全（GRAS）成分。 糖尿病前期折磨着8600万美国人，最近上升到300多万人。 每年仅在美国就有新病例。糖尿病前期患者很可能在10年内成为糖尿病患者，因为 许多患有前驱糖尿病的人没有症状，并且不坚持生活方式和饮食改变或药物治疗。 治疗根据疾病预防控制中心的数据，每10个有前驱糖尿病的美国人中就有9个不知道自己有前驱糖尿病阿坝 补充是一种安全无毒的方法，可以改善小鼠、大鼠和人类的血糖控制， 有效剂量低至1 μg/kg，无副作用。这个快速通道提案的目标是将阿坝发展为 一种控制血糖的药用食品成分。 SBIR快速通道I期申请的具体目标是： AIM 1.探讨了日粮阿坝在鸡骨骼肌中的作用机制和细胞特异性， 小鼠我们将研究ABA诱导的骨骼肌细胞中LANCL 2信号的差异， 糖尿病我们将采用LANCL 2条件性敲除动物来解决阿坝的细胞特异性效应。 AIM 2.表征人类中LANCL 2依赖性机制的翻译潜力 原代骨骼肌细胞在阿坝或媒介物处理的条件下，有或没有siRNA/CRISP LANCL 2，我们将评估GLUT 4易位，葡萄糖摄取和氧化，以及糖原合成。 过渡期的作用是：阿坝依赖于LANCL 2的肌肉特异性表达，阿坝诱导LANCL 2的表达。 增加小鼠和原代人肌肉细胞的离体培养物中葡萄糖的摄取和代谢。 SBIR快速通道第二阶段申请的具体目标是： AIM 3.在糖尿病前期受试者中进行为期14天的人体临床研究，以评估阿坝的作用 对葡萄糖稳态和耐受性的影响使用两组、随机、安慰剂对照 交叉试验，我们将评估阿坝（95 μg，每日两次）如何影响骨骼肌胰岛素敏感性， 肌肉高胰岛素，正葡萄糖钳夹，结合经皮肌肉活检， 在增强的胰岛素敏感性中直接询问LANCL 2活化和GLUT 4易位。 商业应用：BTI将产生阿坝在维持健康葡萄糖水平方面的声明。阿坝 到2018年，这些产品可能会颠覆90亿美元的医疗食品、150亿美元的功能水和580亿美元的糖尿病市场。