Abscisic Acid Improves Insulin Action on Glycemia in Insulin-Deficient Mouse Models of Type 1 Diabetes

Abstract

Background: 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). Methods: Mice were rendered diabetic with streptozotocin and the effect of ABA administration, alone or with insulin, was tested on glycemia. Results: 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. Conclusion: 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.

The ABA-LANCL1/2 Hormone-Receptors System Protects H9c2 Cardiomyocytes from Hypoxia-Induced Mitochondrial Injury via an AMPK- and NO-Mediated Mechanism

“…Defective endogenous ABA has been observed in both T1D and T2D [ 12 , 55 ], suggesting that endogenous ABA deficiency may play a role in the pathogenesis of glucose intolerance due to insulin deficiency or resistance. Indeed, oral ABA has been shown to improve glucose tolerance in borderline and prediabetic subjects [ 56 , 57 ] and to improve insulin sensitivity in murine models of T1D [ 58 ]. From the data presented here, we hypothesize that the impaired endogenous ABA function occurring in diabetes could contribute to the reduced resilience of cardiomyocytes to the ultimate stressor of these cells, i.e., hypoxia.…”

Beneficial Contribution to Glucose Homeostasis by an Agro-Food Waste Product Rich in Abscisic Acid: Results from a Randomized Controlled Trial

“…Eventually, the main consequence of this process could be represented by an increase in GLUT4 expression and glycogen accumulation [ 13 , 31 ]. AMPK also represents an upstream positive regulator of p38 MAPK [ 32 ], which has been attributed its ability to promote PPAR-γ phosphorylation on Ser122, therefore preventing PPAR-γ-induced inhibition of GLUT4 expression [ 13 , 33 , 34 ]. Altogether, these observations of the non-overlapping signaling pathways and the metabolic effects of ABA and insulin suggest a role of ABA as the first hormonal actor in the glycemic response.…”

The ABA/LANCL Hormone/Receptor System in the Control of Glycemia, of Cardiomyocyte Energy Metabolism, and in Neuroprotection: A New Ally in the Treatment of Diabetes Mellitus?

“…Thus, the improvement of glycemic control in the ABA-treated animals was not attributed to higher endogenous insulin levels but rather to the glycemia-lowering action of ABA via an increased skeletal muscle glucose uptake. Furthermore, ABA-treated mice had increased expression of the insulin receptor in skeletal muscle, suggesting an improved action of residual endogenous insulin [ 32 ].…”

“…In the SHD protocol, ABA alone could not substitute for insulin under conditions of total insulin deficiency when glycemia increased to higher than 500 mg/dL, but it improved the effect of exogenous insulin, when the dose of the peptide hormone was insufficient to restore euglycemia [ 32 ].…”