Effects of Abscisic Acid on Insulin Sensitivity

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 andamp; 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 ofmice. We will investigate differential ABA-induced LANCL2 signaling in skeletal muscle cells duringdiabetes. 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 humanprimary skeletal muscle cells. Under ABA or vehicle treated conditions, with or without siRNA/CRISPLANCL2, 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 ABAon glucose homeostasis and tolerability. Using a two group, randomized, placebo controlledcrossover trial, we will evaluate how ABA (95 μg) twice daily effects insulin sensitivity within skeletalmuscle by the hyperinsuliemic, euglycemic clamp, combined with percutaneous muscle biopsies todirectly 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.Abscisic acid (ABA) has demonstrated outstanding efficacy in improving glycemic control, but even though its concentration in some fruits is high, the amount of ABA available in the normal diet alone fails to provide an effective control of blood sugar levels. Given that 34% of adults in the U.S. have metabolic syndrome, obesity, prediabetes, or diabetes; and they also have low levels of ABA in metabolic pools, an ABA-containing medical food developed under this SBIR could address the overlying health problems of over 100 million US consumers with a market exceeding $58B annually by 2018 and could also disrupt the $9B medical foods and 15B functional water markets.