β cell membrane remodelling and procoagulant events occur in inflammation‐driven insulin impairment: a GLP ‐1 receptor dependent and independent control
| Autor: | Céline Gleizes, Guillaume Kreutter, Mohamad Kassem, Malak Abbas, Andrei Alexandru Constantinescu, Laurence Kessler, Julie Boisramé-Helms, Blandine Yver, Florence Toti |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
insulin medicine.medical_specialty MAP Kinase Signaling System medicine.medical_treatment β cell Inflammation Biology Exocytosis Glucagon-Like Peptide-1 Receptor Thromboplastin 03 medical and health sciences Cell-Derived Microparticles Glucagon-Like Peptide 1 Insulin-Secreting Cells Internal medicine medicine Animals Protein kinase A Receptor Lipid raft Cells Cultured Glucagon-like peptide 1 receptor microparticles Caspase 3 Liraglutide Insulin Cell Membrane ion channels Original Articles Cell Biology tissue factor Cyclic AMP-Dependent Protein Kinases Peptide Fragments lipid raft Rats 030104 developmental biology Endocrinology GLP‐1 receptor Hyperglycemia Molecular Medicine Original Article medicine.symptom SNARE Proteins medicine.drug |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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