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.
- MeSH
- Insulin-Secreting Cells metabolism MeSH
- Cell Line MeSH
- Chromatography, Liquid MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Mass Spectrometry MeSH
- Insulin metabolism MeSH
- Microscopy, Confocal MeSH
- Mice MeSH
- Receptors, G-Protein-Coupled genetics metabolism MeSH
- Insulin Secretion MeSH
- Serum Albumin, Bovine pharmacology MeSH
- Signal Transduction physiology MeSH
- Calcium metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH