論文 - 詳細
| RRC ID | 68986 |
|---|---|
| 著者 | Maeda A, Kai K, Ishii M, Ishii T, Akagawa M. |
| タイトル | Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay mice. |
| ジャーナル | Mol Nutr Food Res |
| Abstract |
SCOPE: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. METHODS AND 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. CONCLUSION:Our results strongly suggest the usefulness of safranal in antidiabetic treatment for type 2 diabetic subjects. |
| 巻・号 | 58(6) |
| ページ | 1177-89 |
| 公開日 | 2014-6-1 |
| DOI | 10.1002/mnfr.201300675 |
| PMID | 24668740 |
| MeSH | Animals Crocus / chemistry Cyclohexenes / pharmacology* Diabetes Mellitus, Type 2 / drug therapy* Female Glucose Intolerance Hypoglycemic Agents / pharmacology Insulin Resistance Male Mice Mice, Inbred Strains Muscle Fibers, Skeletal / cytology* Muscle Fibers, Skeletal / drug effects Myoblasts / drug effects Myoblasts / metabolism Plant Extracts / pharmacology* Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism* Signal Transduction Terpenes / pharmacology* |
| IF | 5.309 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) |