Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling
| Autor: | Vanessa Lavallard, Antoine Goujon, Thierry Brun, Sabrina Granziera, Aurélien Roux, Adai Colom, Lucie Oberhauser, Stefan Matile, Pierre Maechler |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Membrane/fluidity Membrane Fluidity Palmitates chemistry.chemical_element 030209 endocrinology & metabolism Calcium Exocytosis Membrane Potentials 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Insulin-Secreting Cells Insulin Secretion Membrane fluidity Animals Insulin Secretion Fatty acids ddc:612 Pancreas Molecular Biology Linolenate Triglycerides Cell Proliferation chemistry.chemical_classification ddc:617 Lipid metabolism Cell Biology Lipid Metabolism Mitochondria Rats src-Family Kinases Glucose 030104 developmental biology Biochemistry Lipotoxicity chemistry ddc:540 Oleic Acid Polyunsaturated fatty acid |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Cell Research, Vol. 1867, No 2 (2020) P. 118619 |
| ISSN: | 0167-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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