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Article Dans Une Revue Journal of Cellular and Molecular Medicine Année : 2016

β cell membrane remodeling and procoagulant events occur in inflammation-driven insulin impairment: A GLP-1 receptor dependent and independent control

Résumé

Inflammation and hyperglycaemia are associated with a prothrombotic state. Cell-derived microparticles (MPs) are the conveyors of active procoagulant tissue factor (TF) and circulate at high concentration in diabetic patients. Liraglutide, a glucagon-like peptide (GLP)-1 analogue, is known to promote insulin secretion and β-cell preservation. In this in vitro study, we examined the link between insulin impairment, procoagulant activity and plasma membrane remodelling, under inflammatory conditions. Rin-m5f β-cell function, TF activity mediated by MPs and their modulation by 1 μM liraglutide were examined in a cell cross-talk model. Methyl-β-cyclodextrine (MCD), a cholesterol depletor, was used to evaluate the involvement of raft on TF activity, MP shedding and insulin secretion as well as Soluble N-éthylmaleimide-sensitive-factor Attachment protein Receptor (SNARE)-dependent exocytosis. Cytokines induced a two-fold increase in TF activity at MP surface that was counteracted by liraglutide. Microparticles prompted TF activity on the target cells and a two-fold decrease in insulin secretion via protein kinase A (PKA) and p38 signalling, that was also abolished by liraglutide. Large lipid raft clusters were formed in response to cytokines and liraglutide or MCD-treated cells showed similar patterns. Cells pre-treated by saturating concentration of the GLP-1r antagonist exendin (9-39), showed a partial abolishment of the liraglutide-driven insulin secretion and liraglutide-decreased TF activity. Measurement of caspase 3 cleavage and MP shedding confirmed the contribution of GLP-1r-dependent and -independent pathways. Our results confirm an integrative β-cell response to GLP-1 that targets receptor-mediated signalling and membrane remodelling pointing at the coupling of insulin secretion and inflammation-driven procoagulant events.
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Dates et versions

hal-01280525 , version 1 (26-01-2023)

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Paternité - Pas d'utilisation commerciale

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Céline Gleizes, Guillaume Kreutter, Malak Abbas, Mohamad Kassem, Andrei Alexandru Constantinescu, et al.. β cell membrane remodeling and procoagulant events occur in inflammation-driven insulin impairment: A GLP-1 receptor dependent and independent control. Journal of Cellular and Molecular Medicine, 2016, 20, pp.231-242. ⟨10.1111/jcmm.12683⟩. ⟨hal-01280525⟩

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