Cell and Tissue Research

, Volume 322, Issue 2, pp 207–215

Free fatty acid receptor 1 (FFA1R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion

  • A. Salehi
  • E. Flodgren
  • N. E. Nilsson
  • J. Jimenez-Feltstrom
  • J. Miyazaki
  • C. Owman
  • B. Olde
Regular Article

Abstract

Free fatty acids (FFA) have generally been proposed to regulate pancreatic insulin release by an intracellular mechanism involving inhibition of CPT-1. The recently de-orphanized G-protein coupled receptor, FFA1R/GPR40, has been shown to be essential for fatty-acid-stimulated insulin release in MIN6 mouse insulinoma cells. The CPT-1 inhibitor, 2-bromo palmitate (2BrP), was investigated for its ability to interact with mouse FFA1R/GPR40. It was found to inhibit phosphatidyl inositol hydrolysis induced by linoleic acid (LA) (100 μM in all experiments) in HEK293 cells transfected with FFA1R/GPR40 and in the MIN6 subclone, MIN6c4. 2BrP also inhibited LA-stimulated insulin release from mouse pancreatic islets. Mouse islets were subjected to antisense intervention by treatment with a FFA1R/GPR40-specific morpholino oligonucleotide for 48 h. Antisense treatment of islets suppressed LA-stimulated insulin release by 50% and by almost 100% when islets were pretreated with LA for 30 min before applying the antisense. Antisense treatment had no effect on tolbutamide-stimulated insulin release. Confocal microscopy using an FFA1R/GPR40-specific antibody revealed receptor expression largely localized to the plasma membrane of insulin-producing cells. Pretreating the islets with LA for 30 min followed by antisense oligonucleotide treatment for 48 h reduced the FFA1R/GPR40 immunoreactivity to background levels. The results demonstrate that FFA1R/GPR40 is inhibited by the CPT-1 inhibitor, 2BrP, and confirm that FFA1R/GPR40 is indeed necessary, at least in part, for fatty-acid-stimulated insulin release.

Keywords

GPR40 Free fatty acid Insulin Pancreatic islet 2-bromo palmitate Mouse (NMRI) 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • A. Salehi
    • 1
  • E. Flodgren
    • 2
  • N. E. Nilsson
    • 2
  • J. Jimenez-Feltstrom
    • 1
  • J. Miyazaki
    • 3
  • C. Owman
    • 2
  • B. Olde
    • 2
  1. 1.Section of Diabetes and EndocrinologyLundSweden
  2. 2.Section of Cellular and Molecular PharmacologyWallenberg Neuroscience CenterLundSweden
  3. 3.Division of Stem Cell Regulation ResearchG6 Osaka University Medical SchoolSuita, OsakaJapan

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