title: Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice.
abstract: METHODS
  Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling by tyrosine dephosphorylation of insulin receptor, and its increased activity and expression is implicated in the pathogenesis of insulin resistance. Hence, PTP1B inhibition is anticipated to improve insulin resistance in type 2 diabetic subjects. The aim of this study was to find a novel PTP1B inhibitor from medicinal food and to evaluate its antidiabetic effects.
  
  
  RESULTS
  We found that saffron (Crocus sativus L.), which is used both as a spice and as a traditional medicine, potently inhibits PTP1B activity. Analyses of saffron extracts demonstrated that safranal, the saffron's aroma compound, is a principal PTP1B inhibitor, and induces a ligand-independent activation of insulin signaling in cultured myotubes. Our data implied that the molecular mechanism underlying the inactivation of PTP1B could be attributed to the covalent modification of the catalytic cysteinyl thiol by safranal through a Michael addition. Furthermore, safranal significantly enhanced glucose uptake through the translocation of glucose transporter 4. We also demonstrated that 2-wk oral administration of 20 mg/kg/day safranal improved impaired glucose tolerance in type 2 diabetic KK-A(y) mice.
  
  
  CONCLUSIONS
  Our results strongly suggest the usefulness of safranal in antidiabetic treatment for type 2 diabetic subjects.
authors.affiliation: Department of Biological Chemistry, Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Maeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kai
authors.forename: Megumi
authors.initials: M
authors.lastname: Ishii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishii
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Akagawa
mesh_terms: D000818:Animals; D027622:Crocus / Q000737:chemistry; D053138:Cyclohexenes / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D018149:Glucose Intolerance; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D053138:Cyclohexenes; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D013729:Terpenes; C087963:safranal; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse
keywords: Diabetes; Insulin resistance; Protein tyrosine phosphatase 1B; Saffron (Crocus sativus L.); Safranal