Abscisic Acid Improves Insulin Action on Glycemia in Insulin-Deficient Mouse Models of Type 1 Diabetes
Mirko Magnone,
Sonia Spinelli,
Giulia Begani,
Lucrezia Guida,
Laura Sturla,
Laura Emionite,
Elena Zocchi
Affiliations
Mirko Magnone
Department of Experimental Medicine, Section of Biochemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy
Sonia Spinelli
Department of Experimental Medicine, Section of Biochemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy
Giulia Begani
Department of Experimental Medicine, Section of Biochemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy
Lucrezia Guida
Department of Experimental Medicine, Section of Biochemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy
Laura Sturla
Department of Experimental Medicine, Section of Biochemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy
Laura Emionite
Animal Facility, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy
Elena Zocchi
Department of Experimental Medicine, Section of Biochemistry, School of Medical and Pharmaceutical Sciences, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy
Abscisic acid (ABA), a plant hormone, has recently been shown to play a role in glycemia regulation in mammals, by stimulating insulin-independent glucose uptake and metabolism in skeletal muscle. The aim of this study was to test whether ABA could improve glycemic control in a murine model of type 1 diabetes (T1D). Mice were rendered diabetic with streptozotocin and the effect of ABA administration, alone or with insulin, was tested on glycemia. Diabetic mice treated with a single oral dose of ABA and low-dose subcutaneous insulin showed a significantly reduced glycemia profile compared with controls treated with insulin alone. In diabetic mice treated for four weeks with ABA, the effect of low-dose insulin on the glycemia profile after glucose load was significantly improved, and transcription both of the insulin receptor, and of glycolytic enzymes in muscle, was increased. Moreover, a significantly increased transcription and protein expression of AMPK, PGC1-α, and GLUT4 was observed in the skeletal muscle from diabetic mice treated with ABA, compared with untreated controls. ABA supplementation in conjunction with insulin holds the promise of reducing the dose of insulin required in T1D, reducing the risk of hypoglycemia, and improving muscle insulin sensitivity and glucose consumption.
