Abscisic acid: a promising molecule in the treatment of type 2 diabetes mellitus and its complications

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar, insulin resistance, and relative insulin insufficiency. Being a life-long condition, T2DM exposes affected subjects to life-threatening sequelae, which typically arise one or more decades after disease onset, consisting of cardiovascular disease, stroke, and diabetic neuropathy, all sustained by the widespread damage to the microcirculation, caused by the metabolic derangement. The number of T2DM patients by 2035 is projected to reach 592 million people worldwide, rising concern among the National Health Care Institutions regarding the sustainability of health care to the increasing T2DM population. For this reason, a concerted effort is underway within the scientific community to meet the demand for innovative therapeutic and preventive strategies for T2DM treatment. While T2DM is a life-long condition, pre-diabetes is reversible: thus, pharmacological and life-style interventions aimed at preventing or delaying the progression of pre-diabetes to the overt disease are currently investigated. Interestingly, the plant hormone abscisic acid (ABA) has been recently identified as a new mammalian hormone involved in the regulation of glycaemia through its receptor LANCL2, paving the way to the potential use of ABA as a new therapeutic in diabetes. Among the currently utilized anti-diabetic drugs, GLP-1 mimetics reduce glycemia and also provide neuro- and cardio-protective effects, which are particularly advantageous in the diabetic patient. The aims of my thesis were the following: i) to investigate the functional cross-talk between GLP-1 and ABA in vitro and in vivo on a rodent whole-body perfusion model, and to investigate the possible neuroprotective role of ABA (I chapter); ii) to investigate the role of the ABA/LANCL2 system in the regulation of glucose uptake, adipogenesis and adipocyte browning in rodent and human adipocytes (II chapter).Parts of the results described in the 1st and 2nd chapter of this thesis have been already published (Bruzzone S et al, Plos One 2015 and Sturla L et al, Biochim Biophys Acta 2017). I performed all the experiments described in this thesis.