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Abscisic acid (ABA) is a hormone with a very long evolutionary history, dating back to the earliest living organisms, of which modern (ABA-producing) cyanobacteria are likely the descendants, well before separation of the plant and animal kingdoms, with a conserved role as a signal regulating cell responses to environmental challenges. In mammals, nanomolar ABA controls the metabolic response to glucose availability by stimulating glucose uptake in skeletal muscle and adipose tissue with an insulin-independent mechanism and increasing energy expenditure in the brown and white adipose tissues. Activation by ABA of AMP-dependent kinase (AMPK), in contrast to the insulin-induced activation of AMPK-inhibiting Akt, is responsible for stimulation of GLUT4-mediated muscle glucose uptake, and for the browning effect on white adipocytes. Intake of micrograms per Kg body weight of ABA improves glucose tolerance in both normal and in borderline subjects and chronic intake of such a dose of ABA improves blood glucose, lipids and morphometric parameters (waist circumference and body mass index) in borderline subjects for prediabetes and the metabolic syndrome. This review summarizes the most recent results obtained in vivo with microgram amounts of ABA, the role of the receptor LANCL2 in the hormone's action and the significance of the endowment by mammals of two different hormones controlling the metabolic response to glucose availability. Finally, open issues in need of further investigation and perspectives for the clinical use of nutraceutical ABA are discussed.

Abscisic Acid: A Conserved Hormone in Plants and Humans and a Promising Aid to Combat Prediabetes and the Metabolic Syndrome