Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis

Metabolism. 2016 Mar;65(3):8-17. doi: 10.1016/j.metabol.2015.10.003. Epub 2015 Nov 2.


Objective: Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect.

Methods: First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer.

Results: OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA-induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it.

Conclusion: These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1.

Keywords: Extracellular acidification rate; GLP-1; GLUTag cells; Oxygen consumption rate; Seahorse extracellular flux analyzer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
  • Cell Line
  • Cell Respiration / drug effects*
  • Electron Transport / drug effects
  • Energy Metabolism / drug effects
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucose / metabolism
  • Glycolysis / drug effects*
  • Mice
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / metabolism
  • Oleic Acid / pharmacology*
  • Oxidative Phosphorylation / drug effects
  • Oxygen Consumption / drug effects
  • Pyruvic Acid / metabolism


  • Oleic Acid
  • Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
  • Pyruvic Acid
  • Glucagon-Like Peptide 1
  • Adenosine Triphosphate
  • Glucose