Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling

Article Article scientifique Article Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling eng 2020 author Oberhauser Lucie 832607 author Granziera Sabrina 887543 author Colom Diego Adai 815331 author Goujon Antoine 858530 author Lavallard Vanessa 772754 author Matile Stefan 0000-0002-8537-8349 129654 author Roux Aurélien 0000-0002-6088-0711 716946 author Brun Thierry 0000-0002-1659-4283 24644 author Maechler Pierre 0000-0002-2005-1433 76515 118619 10.1016/j.bbamcr.2019.118619 31816355 0167-4889 https://linkinghub.elsevier.com/retrieve/pii/S0167488919302277 Chronic exposure to elevated levels of glucose and free fatty acids impairs beta-cell function, leading to insulin secretion defects and eventually beta-cell failure. Using a semi-high throughput approach applied to INS-1E beta-cells, we tested multiple conditions of chronic exposure to basal, intermediate and high glucose, combined with saturated versus mono- and polyunsaturated fatty acids in order to assess cell integrity, lipid metabolism, mitochondrial function, glucose-stimulated calcium rise and secretory kinetics. INS-1E beta-cells were cultured for 3 days at different glucose concentrations (5.5, 11.1, 25 mM) without or with BSA-complexed 0.4 mM saturated (C16:0 palmitate), monounsaturated (C18:1 oleate) or polyunsaturated (C18:2 linoleate, C18:3 linolenate) fatty acids, resulting in 0.1–0.5 μM unbound fatty acids. Accumulation of triglycerides in cells exposed to fatty acids was glucose-dependent, oleate inducing the strongest lipid storage and protecting against glucose-induced cytotoxicity. The combined chronic exposure to both high glucose and either palmitate or oleate altered mitochondrial function as well as glucose-induced calcium rise. This pattern did not directly translate at the secretory level since palmitate and oleate exhibited distinct effects on the first and the second phases of glucose-stimulated exocytosis. Both fatty acids changed the activity of kinases, such as the MODY-associated BLK. Additionally, chronic exposure to fatty acids modified membrane physicochemical properties by increasing membrane fluidity, oleate exhibiting larger effects compared to palmitate. Chronic fatty acids differentially and specifically exacerbated some of the glucotoxic effects, without promoting cytotoxicity on their own. Each of the tested fatty acids functionally modified INS-1E beta-cell, oleate inducing the strongest effects. Fatty acids Glucose Insulin Membrane/fluidity Pancreas Lipotoxicity Dewey 540 Dewey 612 Dewey 617 Swiss National Science Foundation NCCR Chemical Biology: Visualisation and Control of Biological Processes Using Chemistry (phase II) 160589 CH Programmes Swiss National Science Foundation Glutamate pathways and metabolic stresses in energy homeostasis 166625 CH Project funding Swiss National Science Foundation Roles de l'elasticite membranaire dans l'endocytose et la cytocinese 149975 CH Projects Swiss National Science Foundation Mechanical coupling between dynamic assembly of protein coats and membrane deformation 173087 CH Projects 36 Département de chimie organique 141 39 Département de biochimie 144 134 Département de physiologie cellulaire et métabolisme 21C 57 Département de chirurgie 222 false 761 Groupe Matile 769 Groupe Roux 357 La transplantation d'îlots de Langerhans 623 402 Mitochondries et métabolisme énergétique 671 Biochimica et Biophysica Acta - Molecular Cell Research 1867 2 a3dfe97a-34cf-4ccc-8683-0e75f53bee04 Article (Published version) Restricted 1-s2.0-S0167488919302277-main.pdf 4044381 application/pdf bf63ca2f-fae2-498c-9a61-c9223cb789df Supplemental data Restricted 1-s2.0-S0167488919302277-mmc2.pdf 1536052 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique Faculté des sciences / Section de chimie et biochimie / Département de biochimie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de chirurgie

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Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling	Biochimica et Biophysica Acta - Molecular Cell Research			2020	563	8

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Granziera, Sabrina