Ibervillea sonorae (Cucurbitaceae) induces the glucose uptake in human adipocytes by activating a PI3K-independent pathway

J Ethnopharmacol. 2014 Mar 28;152(3):546-52. doi: 10.1016/j.jep.2014.01.041. Epub 2014 Feb 15.

Abstract

Ethnopharmacological relevance: Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE).

Materials and methods: Non-toxic ISE concentrations were assayed on the glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques.

Results: ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 µg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 µg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid.

Conclusion: Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independent pathway and without proadipogenic effects.

Keywords: 2-NBDG uptake; 3T3 Adipogenesis; Human adipogenesis; Ibervillea sonorae (Cucurbitaceae); Insulin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Animals
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cucurbitaceae / chemistry*
  • Dose-Response Relationship, Drug
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Insulin Resistance
  • Medicine, Traditional
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Signal Transduction / drug effects
  • Spectrophotometry

Substances

  • Hypoglycemic Agents
  • Insulin
  • Plant Extracts
  • Phosphatidylinositol 3-Kinases
  • Glucose