Effects of Abscisic Acid on Insulin Sensitivity

脱落酸对胰岛素敏感性的影响 生物治疗公司(BTI)是弗吉尼亚理工大学的一家剥离出来的公司，正在为 个性化营养。BTI已经批准了弗吉尼亚理工大学的11项专利申请，这些申请与新的 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(ABA)抗糖尿病作用的重大知识产权(IP)。我们开发了ABA 无花果提取物(ABAlife™)，并将其确立为通常被认为是安全的(GRAS)成分。 意义和产品：糖尿病前期困扰着8600万美国人，最近上升到300多万人 仅在美国每年就有新病例。糖尿病前期患者很可能在10年内患上糖尿病，因为 许多糖尿病前期患者没有症状，不坚持改变生活方式和饮食或药物治疗 治疗。根据美国疾病控制与预防中心的数据，每10名患有糖尿病前期的美国人中，有9人不知道自己患有糖尿病。膳食ABA 补充剂是一种安全无毒的方法，可以改善患有糖尿病的小鼠、大鼠和人类的血糖控制。 有效剂量低至1微克/公斤，无副作用。这项快速通道提案的目标是将ABA发展为 一种控制血糖的药用食品配料。 SBIR快速通道第一阶段应用的具体目标是： 目的1.验证饲料中ABA对小鼠骨骼肌的作用机制和细胞特异性。 老鼠。我们将研究ABA在骨骼肌细胞中诱导的LANCL2信号的差异 糖尿病。我们将使用LANCL2条件性基因敲除动物来解决ABA的细胞特异性效应。 目的2.研究LANCL2依赖机制在人类中的翻译潜能 原代骨骼肌细胞。在ABA或载体处理条件下，使用或不使用siRNA/CRISP LANCL2，我们将评估GLUT4易位、葡萄糖摄取和氧化以及糖原合成。 转变的里程碑是：ABA依赖于肌肉特异性表达的LANCL2和ABA诱导 增加小鼠对葡萄糖的摄取和代谢，以及原代人类肌肉细胞的体外培养。 SBIR快车道第二阶段应用的具体目标是： 目的3.在糖尿病前期受试者中进行为期14天的临床研究，以评估ABA的效果 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，我们将评估每天两次的阿巴(95μg)对骨骼内胰岛素敏感性的影响 肌肉经高胰岛素、正血糖钳夹结合经皮肌肉活组织检查 直接询问LANCL2激活和GLUT4易位在胰岛素敏感性增强中的作用。 商业应用：BTI将提出ABA在维持健康血糖水平方面的索赔。脱落酸 到2018年，这些产品可能会扰乱价值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。

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.