Ursolic acid and its derivative inhibit protein tyrosine phosphatase 1B, enhancing insulin receptor phosphorylation and stimulating glucose uptake

Biochim Biophys Acta. 2006 Oct;1760(10):1505-12. doi: 10.1016/j.bbagen.2006.05.009. Epub 2006 Jun 7.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a key element in the negative regulation of the insulin signaling pathway and may play an important role in diabetes and obesity. We identified ursolic acid, a natural pentacyclic triterpenoid that occurs widely in traditional Chinese medicinal herbs, as an inhibitor of PTP1B by screening an extract library of the traditional Chinese medicinal herbs used a diabetes clinic. By modifying urosolic acid, we designed and synthesized a derivative with a K(i) of 283 nM. As competitive inhibitors of PTP1B, ursolic acid and its derivative also inhibit T-cell protein tyrosine phosphatase and src homology phosphatase-2 but not leucocyte antigen-related phosphatase or protein tyrosine phosphatase alpha and epsilon, which are all possibly involved in the insulin pathway. The ursolic acid derivative enhanced insulin receptor phosphorylation in CHO/hIR cells and stimulate glucose uptake in L6 myotubes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Drugs, Chinese Herbal / pharmacology
  • Glucose / metabolism*
  • Humans
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Phosphorylation
  • Protein Phosphatase 2
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Rats
  • Receptor, Insulin / metabolism*
  • Triterpenes / pharmacology*

Substances

  • Drugs, Chinese Herbal
  • Triterpenes
  • UA 0713
  • Phenylalanine
  • Receptor, Insulin
  • Protein Phosphatase 2
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Ptpn1 protein, rat
  • Glucose
  • ursolic acid