TY - JOUR
T1 - Endogenous fatty acids are essential signaling factors of pancreatic B-cells and insulin secretion
AU - Hauke, Sebastian
AU - Keutler, Kaya
AU - Phapale, Prasad
AU - Yushchenko, Dmytro A.
AU - Schultz, Carsten
N1 - Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/10
Y1 - 2018/10
N2 - The secretion of insulin from b-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 b-cell medium by stringent washing or by the application of FA-free (FAF) BSA immediately reduced glucose-induced oscillations of cytosolic Ca 2+ ([Ca 2+ ] i oscillations) in MIN6 cells and mouse primary b-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. [Ca 2+ ] 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 b-cell activity and insulin secretion.
AB - The secretion of insulin from b-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 b-cell medium by stringent washing or by the application of FA-free (FAF) BSA immediately reduced glucose-induced oscillations of cytosolic Ca 2+ ([Ca 2+ ] i oscillations) in MIN6 cells and mouse primary b-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. [Ca 2+ ] 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 b-cell activity and insulin secretion.
UR - http://www.scopus.com/inward/record.url?scp=85054776125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054776125&partnerID=8YFLogxK
U2 - 10.2337/db17-1215
DO - 10.2337/db17-1215
M3 - Article
C2 - 29748290
AN - SCOPUS:85054776125
SN - 0012-1797
VL - 67
SP - 1986
EP - 1998
JO - Diabetes
JF - Diabetes
IS - 10
ER -