Endogenous Fatty Acids Are Essential Signaling Factors of Pancreatic β-Cells and Insulin Secretion

Sebastian Hauke, Kaya Keutler, Prasad Phapale, Dmytro A. Yushchenko, Carsten Schultz

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1986-1998
Number of pages13
JournalDiabetes
Volume67
Issue number10
DOIs
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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