Endogenous Fatty Acids Are Essential Signaling Factors of Pancreatic β-Cells and Insulin Secretion
| العنوان: | Endogenous Fatty Acids Are Essential Signaling Factors of Pancreatic β-Cells and Insulin Secretion |
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| المؤلفون: | Prasad Phapale, Carsten Schultz, Sebastian Hauke, Kaya Keutler, Dmytro A. Yushchenko |
| المصدر: | Diabetes. 67:1986-1998 |
| بيانات النشر: | American Diabetes Association, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Enzyme-Linked Immunosorbent Assay, 030209 endocrinology & metabolism, Endogeny, Mass Spectrometry, Cell Line, Receptors, G-Protein-Coupled, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin-Secreting Cells, Free fatty acid receptor 1, Insulin Secretion, Internal Medicine, Extracellular, medicine, Animals, Insulin, Secretion, Receptor, Microscopy, Confocal, Chemistry, Serum Albumin, Bovine, Elaidic acid, 030104 developmental biology, Biochemistry, Liberation, Calcium, Female, Chromatography, Liquid, Signal Transduction |
| الوصف: | The secretion of insulin from β-cells depends on extracellular factors, in particular glucose and other small molecules, some of which act on G-protein–coupled receptors. Fatty acids (FAs) have been discussed as exogenous secretagogues of insulin for decades, especially after the FA receptor GPR40 (G-protein–coupled receptor 40) was discovered. However, the role of FAs as endogenous signaling factors has not been investigated until now. In the present work, we demonstrate that lowering endogenous FA levels in β-cell medium by stringent washing or by the application of FA-free (FAF) BSA immediately reduced glucose-induced oscillations of cytosolic Ca2+ ([Ca2+]i oscillations) in MIN6 cells and mouse primary β-cells, as well as insulin secretion. Mass spectrometry confirmed BSA-mediated removal of FAs, with palmitic, stearic, oleic, and elaidic acid being the most abundant species. [Ca2+]i oscillations in MIN6 cells recovered when BSA was replaced by buffer or as FA levels in the supernatant were restored. This was achieved by recombinant lipase–mediated FA liberation from membrane lipids, by the addition of FA-preloaded FAF-BSA, or by the photolysis of cell-impermeant caged FAs. Our combined data support the hypothesis of FAs as essential endogenous signaling factors for β-cell activity and insulin secretion. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8558c6a0b0e8d25ca7aec697bf9e133bTest https://doi.org/10.2337/db17-1215Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8558c6a0b0e8d25ca7aec697bf9e133b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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