(E)-9-oxooctadec-10-en-12-ynoic acid from Ixora brachiata Roxb. increases glucose uptake in L6 myotubes by activating the PI3K pathway

Fitoterapia. 2016 Oct:114:26-33. doi: 10.1016/j.fitote.2016.08.004. Epub 2016 Aug 10.

Abstract

In an attempt to discover new scaffolds for anti-diabetic activity from plants, we screened extracts from Ixora brachiata Roxb. for their effect on glucose uptake in L6 myotubes. The petroleum (PE) extract of the plant showed a significant increase in insulin stimulated glucose uptake by L6 myotubes. The bioactivity guided fractionation of the crude extract yielded a compound (E)-9-oxooctadec-10-en-12-ynoic acid (OEA). The compound induced a dose dependent increase in insulin stimulated glucose uptake in L6 myotubes with an EC50 of 22.96μM. OEA also increased the phosphorylation of IRS-1, Akt and AS160 leading to increased GLUT4 translocation to the plasma membrane indicating that it promotes insulin stimulated glucose uptake in L6 myotubes by activating the PI3K pathway.

Keywords: (E)-9-oxooctadec-10-en-12-ynoic acid; Akt; GLUT4; Ixora brachiata; L6 myotubes.

MeSH terms

  • Animals
  • Cells, Cultured
  • Diynes / isolation & purification
  • Diynes / pharmacology*
  • Fatty Acids, Unsaturated / isolation & purification
  • Fatty Acids, Unsaturated / pharmacology*
  • GTPase-Activating Proteins / metabolism
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / metabolism
  • Insulin / pharmacology
  • Insulin Receptor Substrate Proteins / metabolism
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rubiaceae / chemistry*
  • Signal Transduction*

Substances

  • (E)-9-oxooctadec-10-en-12-ynoic acid
  • Diynes
  • Fatty Acids, Unsaturated
  • GTPase-Activating Proteins
  • Glucose Transporter Type 4
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Plant Extracts
  • Slc2a4 protein, rat
  • TBC1D4 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glucose