title: Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.
abstract: Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.
authors.affiliation: College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, South Korea.
authors.forename: Changkeun
authors.initials: C
authors.lastname: Kang
authors.forename: Hyunkyoung
authors.initials: H
authors.lastname: Lee
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Jung
authors.forename: Ramin
authors.initials: R
authors.lastname: Seyedian
authors.forename: MiNa
authors.initials: M
authors.lastname: Jo
authors.forename: Jehein
authors.initials: J
authors.lastname: Kim
authors.forename: Jong-Shu
authors.initials: JS
authors.lastname: Kim
authors.forename: Euikyung
authors.initials: E
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D027622:Crocus / Q000737:chemistry*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases; D005947:Glucose