Scientific Publications

From Magnone M et al., FASEB J. 2015 Dec;29(12):4783-93. doi: 10.1096/fj.15-277731. Epub 2015 Aug 4

“Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans”

Abstract

[:it]2-Cis,4-trans-abscisic acid (ABA) is a plant hormone that is present also in animals. Several lines of evidence suggest that ABA contributes to the regulation of glycemia in mammals: nanomolar ABA stimulates insulin release from β-pancreatic cells and glucose transporter-4-mediated glucose uptake by myoblasts and adipocytes in vitro; plasma ABA increases in normal human subjects, but not in diabetic patients, after a glucose load for an oral glucose tolerance test (OGTT). The presence of ABA in fruits prompted an exploration of the bioavailability of dietary ABA and the effect of ABA-rich fruit extracts on glucose tolerance. Rats underwent an OGTT, with or without 1 µg/kg ABA, either synthetic or present in a fruit extract. Human volunteers underwent an OGTT or a standard breakfast and lunch, with or without a fruit extract, yielding an ABA dose of 0.85 or 0.5 µg/kg, respectively. Plasma glucose, insulin, and ABA were measured at different time points. Oral ABA at 0.5-1 µg/kg significantly lowered glycemia and insulinemia in rats and in humans. Thus, the glycemia-lowering effect of low-dose ABA in vivo does not depend on an increased insulin release. Low-dose ABA intake may be proposed as an aid to improving glucose tolerance in patients with diabetes who are deficient in or resistant to insulin.

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From Magnone M et al, Nutrients 2018,Oct 12; 10(10). doi:10.3390/nu10101495

Chronic Intake of Micrograms of Abscisic Acid Improves Glycemia and Lipidemia in a Human Study and in High-Glucose Fed Mice

Abstract

We tested the effect of chronic low-dose abscisic acid (ABA), a phytohormone-regulating human glucose tolerance, on the metabolic parameters that are dysregulated in prediabetes and metabolic syndrome (MS).Ten healthy subjects received 1 µg ABA/Kg body weight (BW)/day as an ABA-rich food supplement: (i) the glycemia profile after a carbohydrate-rich meal, with or without supplement, was compared; (ii) fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), and body mass index (BMI) after 75 days of daily supplementation of a habitual Mediterranean diet were compared with starting values.CD1 mice were fed a high-glucose diet with or without synthetic ABA (1 µg/Kg BW) for 4 months and the same parameters investigated in the human study were compared. The food supplement significantly reduced the area under the curve of glycemia after a carbohydrate-rich meal and FBG, HbA1c, TC, and BMI after chronic treatment. ABA-treated mice showed a significant reduction of HbA1c, TC, and body weight gain compared with untreated controls. The combined results from the human and murine studies allow us to conclude that the observed improvement of the metabolic parameters can be attributed to ABA and to advocate the use of ABA-containing food supplements in prediabetes and/or MS.

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From Magnone M et al, Sci Rep. 2020 Jan 29;10(1):1454. doi: 10.1038/s41598-020-58206-0.

Insulin-independent stimulation of skeletal muscle glucose uptake by low-dose abscisic acid via AMPK activation

Abstract

Abscisic acid (ABA) is a plant hormone active also in mammals where it regulates, at nanomolar concentrations, blood glucose homeostasis. Here we investigated the mechanism through which low-dose ABA controls glycemia and
glucose fate. ABA stimulated uptake of the fluorescent glucose analog 2-NBDG by L6, and of [18F]-deoxy-glucose (FDG) by mouse skeletal muscle, in the absence of insulin, and both effects were abrogated by the specific AMPK inhibitor dorsomorphin. In L6, incubation with ABA increased phosphorylation of AMPK and upregulated PGC-1α expression. LANCL2 silencing reduced all these ABA-induced effects. In vivo, low-dose oral ABA stimulated glucose uptake and storage in the skeletal muscle of rats undergoing an oral glucose load, as detected by micro-PET. Chronic treatment with ABA significantly improved the
AUC of glycemia and muscle glycogen content in CD1 mice exposed to a
high-glucose diet. Finally, both acute and chronic ABA treatment
of hypoinsulinemic TRPM2-/- mice ameliorated the glycemia profile and increased
muscle glycogen storage. Altogether, these results suggest that low-dose oral
ABA might be beneficial for pre-diabetic and diabetic subjects by increasing
insulin-independent skeletal muscle glucose disposal through an AMPK-mediated
mechanism.

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from Magnone M et al, Nutrients 2020 Jun 9;12(6):1724. doi: 10.3390/nu12061724.

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

Abstract

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 e_ect 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 di_erent 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.

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