β cell membrane remodelling and procoagulant events occur in inflammation‐driven insulin impairment: a GLP ‐1 receptor dependent and independent control
| العنوان: | β cell membrane remodelling and procoagulant events occur in inflammation‐driven insulin impairment: a |
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| المؤلفون: | Céline Gleizes, Guillaume Kreutter, Mohamad Kassem, Malak Abbas, Andrei Alexandru Constantinescu, Laurence Kessler, Julie Boisramé-Helms, Blandine Yver, Florence Toti |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Wiley, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27ecd0f2939bd7acc802504871436ed3Test https://doi.org/10.1111/jcmm.12683Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....27ecd0f2939bd7acc802504871436ed3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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