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Progetto vincitore della Borsa di Studio SISA 2016 - C. Barale

Glucagon-like peptide 1 effects on platelets in type 2 diabetes mellitus and hypercholesterolemia: putative role of a lipid-lowering therapy

Cristina Barale

Abstract:

Metabolic and hormonal changes characterizing Type 2 Diabetes Mellitus (T2DM) are involved in the pathogenesis of the altered platelet function. Glucagon-like Peptide 1 (GLP-1) is an incretin hormone which exerts pivotal effects on glucose control and also influences cardiovascular system. No information exist on the role of GLP-1 on peculiar aspects of platelet functions in T2DM. Furthermore, data concerning the role of hypercholesterolemia per se in affecting platelet sensitivity to GLP-1 effects are unknown. We have recently found that normally GLP-1 in vitro decreases platelet reactivity and this effect is impaired in platelets from T2DM subjects.

The study will be structured in different protocols aimed at verifying: i) whether the GLP-1-based therapy in T2DM influences platelet reactivity to the pro- and antiaggregating agents; b) whether hypecholesterolemia -in the absence of hyperglycemia- reduces GLP-1 action on platelet function; c) whether the correction of hypercholesterolemia, in subjects affected by primary hypercholesterolemia, improves GLP-1 effects on platelets. In particular, at baseline and after 2 weeks and 3 months of treatment with the GLP-1 analogue Liraglutide in T2DM (n=50) or with the lipid-lowering drug simvastatin in subjects affected by primary hypercholesterolemia (n=50), we will measure parameters of: i) metabolic homeostasis; ii) in vivo platelet activation; iii)inflammation; iv)platelet responses by aggregation tests, evaluation of activation of the inhibitory pathways nitric oxide/cGMP/PKG and cAMP/PKA, activation of the aggregating pathways PI/3K and MAPK and oxidative stress. Moreover, we will also establish whether T2DM and hypercholesterolemia show a normal expression of GLP-1 receptor on platelet surface.

Thus, the project will add new evidences on the role of GLP-1 on platelets in T2DM and eventually to provide an useful therapeutic option to improve also vascular GLP-1 effects.

Presentazione del progetto vincitore di Borsa di Studio SISA - 2016