The P21-activated kinase PAK4 is implicated in fatty-acid potentiation of insulin secretion downstream of free fatty acid receptor 1

Islets. 2016 Nov;8(6):157-164. doi: 10.1080/19382014.2016.1243191. Epub 2016 Oct 4.


Free fatty acid receptor 1 (FFA1/GPR40) plays a key role in the potentiation of glucose-stimulated insulin secretion by fatty acids in pancreatic β cells. We previously demonstrated that GPR40 signaling leads to cortical actin remodeling and potentiates the second phase of insulin secretion. In this study, we examined the role of p21 activated kinase 4 (PAK4), a known regulator of cytoskeletal dynamics, in GPR40-dependent potentiation of insulin secretion. The fatty acid oleate induced PAK4 phosphorylation in human islets, in isolated mouse islets and in the insulin secreting cell line INS832/13. However, oleate-induced PAK4 phosphorylation was not observed in GPR40-null mouse islets. siRNA-mediated knockdown of PAK4 in INS832/13 cells abrogated the potentiation of insulin secretion by oleate, whereas PAK7 knockdown had no effect. Our results indicate that PAK4 plays an important role in the potentiation of insulin secretion by fatty acids downstream of GPR40.

Keywords: Fatty acids; G protein-coupled receptor 40; Insulin secretion; P21-activated kinase; free fatty acid receptor 1.

MeSH terms

  • Animals
  • Cell Line
  • Glucose / pharmacology
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Knockout
  • Oleic Acid / pharmacology*
  • Phosphorylation
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • p21-Activated Kinases / metabolism*


  • FFAR1 protein, human
  • Insulin
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Oleic Acid
  • PAK4 protein, human
  • p21-Activated Kinases
  • Glucose

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