Title : Role of the abscisic acid/LANCL system in glycemic control: A promising aid to combat diabetes and related metabolic syndrome
Abscisic acid (ABA) is an isoprenoid hormone with a very long evolutionary history and the only known hormone common to the vegetal and animal kingdoms, with a conserved role as a signal regulating cell responses to environmental challenge. Nanomolar ABA is also present and active in mammals where it controls the function of many cell types through its receptors LANCL1 and LANCL2. In rat and murine myoblasts, LANCL receptors similarly stimulate both basal and ABA-triggered glucose uptake with an insulin-independent mechanism, activate mRNA levels and protein expression of the glucose transporters GLUT1 and GLUT4 and the signaling proteins AMPK/PGC-1α/Sirt1, stimulate mitochondrial respiration and the expression of the skeletal muscle (SM) uncoupling proteins sarcolipin and UCP3. In human adipocytes overexpressing ABA receptors, glucose transport, expression of genes related to browning, oxidative consumption, mitochondrial biogenesis, respiratory uncoupling and AMPK/PGC-1α/Sirt1 pathway is increased after adipocyte differentiation and further increases upon ABA treatment.
In vivo, low-dose oral ABA stimulated glucose uptake and storage in the skeletal muscle and brown adipose tissue 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 and both acute and chronic ABA treatment of hypoinsulinemic mice ameliorated the glycemia profile and increased muscle glycogen storage. Moreover, LANCL2 knock-out mice have a reduced glucose tolerance compared to WT, but they do respond to chronic ABA treatment (1 µg/kg BW/day) with an improved glycemia response to glucose load and an increased skeletal muscle transcription of GLUT4, GLUT1 (20-fold) and of the AMPK/PGC-1a/Sirt1 axis.
In human, 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 lipids and morphometric parameters in borderline subjects for prediabetes and the metabolic syndrome. Altogether, these results suggest that low-dose oral ABA might be beneficial for pre-diabetic and T2D diabetic subjects by increasing insulin-independent skeletal muscle glucose disposal through an AMPK-mediated mechanism.
Finally, in mice were rendered diabetic with streptozotocin 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 of the insulin receptor, glycolytic enzymes, AMPK, PGC1-α, and GLUT4 in skeletal muscle, was increased. 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.
Audience Take Away:
- The audience will learn about the new mammalian hormone abscisic acid and its role in the glycemic control.
- The audience will be able to understand the possible benefits of treatment with ABA of pre-diabetic subjects, T1D and T2D patients.
- The audience shall explore the research of new nutraceutical supplements: these molecules could be effective and good co-adjuvants, along with diet and drug treatment, in improving chronic degenerative disease such as type 2 diabetes mellitus.